NM_002291.3:c.3065A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002291.3(LAMB1):c.3065A>G(p.Gln1022Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 1,612,288 control chromosomes in the GnomAD database, including 329,260 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33752 hom., cov: 32)

Exomes 𝑓: 0.63 ( 295508 hom. )

Consequence

LAMB1
NM_002291.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.13

Publications

42 publications found

Variant links:

Genes affected

LAMB1 (HGNC:6486): (laminin subunit beta 1) Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Laminins are composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively) and they form a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene. Several isoforms of each chain have been described. Different alpha, beta and gamma chain isomers combine to give rise to different heterotrimeric laminin isoforms which are designated by Arabic numerals in the order of their discovery, i.e. alpha1beta1gamma1 heterotrimer is laminin 1. The biological functions of the different chains and trimer molecules are largely unknown, but some of the chains have been shown to differ with respect to their tissue distribution, presumably reflecting diverse functions in vivo. This gene encodes the beta chain isoform laminin, beta 1. The beta 1 chain has 7 structurally distinct domains which it shares with other beta chain isomers. The C-terminal helical region containing domains I and II are separated by domain alpha, domains III and V contain several EGF-like repeats, and domains IV and VI have a globular conformation. Laminin, beta 1 is expressed in most tissues that produce basement membranes, and is one of the 3 chains constituting laminin 1, the first laminin isolated from Engelbreth-Holm-Swarm (EHS) tumor. A sequence in the beta 1 chain that is involved in cell attachment, chemotaxis, and binding to the laminin receptor was identified and shown to have the capacity to inhibit metastasis. [provided by RefSeq, Aug 2011]

LAMB1 Gene-Disease associations (from GenCC):

cobblestone lissencephaly without muscular or ocular involvement
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, PanelApp Australia, Genomics England PanelApp, G2P

LAMB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.994713E-7).

BP6

Variant 7-107953544-T-C is Benign according to our data. Variant chr7-107953544-T-C is described in ClinVar as Benign. ClinVar VariationId is 380837.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMB1	NM_002291.3 link	c.3065A>G	p.Gln1022Arg	missense_variant	Exon 22 of 34	ENST00000222399.11	NP_002282.2	P07942Q8TAS6
LAMB1	XM_047420359.1 link	c.3065A>G	p.Gln1022Arg	missense_variant	Exon 22 of 28		XP_047276315.1
LAMB1	XM_047420360.1 link	c.3065A>G	p.Gln1022Arg	missense_variant	Exon 22 of 25		XP_047276316.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMB1	ENST00000222399.11 link	c.3065A>G	p.Gln1022Arg	missense_variant	Exon 22 of 34	1	NM_002291.3	ENSP00000222399.6		P07942

Frequencies

GnomAD3 genomes

AF:

0.665

AC:

100994

AN:

151960

Hom.:

33715

Cov.:

show subpopulations

Gnomad AFR

AF:

0.708

Gnomad AMI

AF:

0.624

Gnomad AMR

AF:

0.654

Gnomad ASJ

AF:

0.686

Gnomad EAS

AF:

0.843

Gnomad SAS

AF:

0.612

Gnomad FIN

AF:

0.681

Gnomad MID

AF:

0.630

Gnomad NFE

AF:

0.628

Gnomad OTH

AF:

0.642

GnomAD2 exomes

AF:

0.647

AC:

162392

AN:

251096

AF XY:

0.641

show subpopulations

Gnomad AFR exome

AF:

0.704

Gnomad AMR exome

AF:

0.625

Gnomad ASJ exome

AF:

0.668

Gnomad EAS exome

AF:

0.832

Gnomad FIN exome

AF:

0.667

Gnomad NFE exome

AF:

0.623

Gnomad OTH exome

AF:

0.630

GnomAD4 exome

AF:

0.634

AC:

925847

AN:

1460210

Hom.:

295508

Cov.:

AF XY:

0.632

AC XY:

459444

AN XY:

726488

show subpopulations

African (AFR)

AF:

0.710

AC:

23720

AN:

33432

American (AMR)

AF:

0.632

AC:

28260

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.669

AC:

17467

AN:

26128

East Asian (EAS)

AF:

0.855

AC:

33914

AN:

39674

South Asian (SAS)

AF:

0.595

AC:

51323

AN:

86202

European-Finnish (FIN)

AF:

0.663

AC:

35388

AN:

53414

Middle Eastern (MID)

AF:

0.560

AC:

3223

AN:

5754

European-Non Finnish (NFE)

AF:

0.625

AC:

693854

AN:

1110554

Other (OTH)

AF:

0.641

AC:

38698

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

16578

33157

49735

66314

82892

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18610

37220

55830

74440

93050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.665

AC:

101087

AN:

152078

Hom.:

33752

Cov.:

AF XY:

0.667

AC XY:

49608

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.709

AC:

29393

AN:

41478

American (AMR)

AF:

0.655

AC:

10005

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.686

AC:

2379

AN:

3470

East Asian (EAS)

AF:

0.842

AC:

4359

AN:

5176

South Asian (SAS)

AF:

0.612

AC:

2952

AN:

4824

European-Finnish (FIN)

AF:

0.681

AC:

7196

AN:

10562

Middle Eastern (MID)

AF:

0.622

AC:

183

AN:

294

European-Non Finnish (NFE)

AF:

0.628

AC:

42695

AN:

67972

Other (OTH)

AF:

0.644

AC:

1357

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

1766

3533

5299

7066

8832

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

802

1604

2406

3208

4010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.641

Hom.:

117846

Bravo

AF:

0.662

TwinsUK

AF:

0.640

AC:

2374

ALSPAC

AF:

0.627

AC:

2417

ESP6500AA

AF:

0.705

AC:

3105

ESP6500EA

AF:

0.625

AC:

5379

ExAC

AF:

0.645

AC:

78257

Asia WGS

AF:

0.743

AC:

2582

AN:

3478

EpiCase

AF:

0.618

EpiControl

AF:

0.623

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Jan 08, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.075

(source)

DANN

Benign

0.29

DEOGEN2

Benign

0.049

.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.25

T;T

MetaRNN

Benign

8.0e-7

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.11

.;N

PhyloP100

-1.1

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.53

N;N

REVEL

Benign

0.091

Sift

Benign

1.0

T;T

Sift4G

Benign

0.67

T;T

Polyphen

0.0

B;B

Vest4

0.031

MPC

0.095

ClinPred

0.0018

GERP RS

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.074

gMVP

0.39

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over