7-107986325-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002291.3(LAMB1):c.462C>T(p.Ser154Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,607,980 control chromosomes in the GnomAD database, including 12,793 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1002 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11791 hom. )

Consequence

LAMB1
NM_002291.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.51

Publications

18 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, Unknown Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Ambry Genetics, Orphanet, ClinGen

LAMB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 7-107986325-G-A is Benign according to our data. Variant chr7-107986325-G-A is described in ClinVar as Benign. ClinVar VariationId is 380836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.51 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002291.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMB1	NM_002291.3	MANE Select	c.462C>T	p.Ser154Ser	synonymous	Exon 6 of 34	NP_002282.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LAMB1	ENST00000222399.11	TSL:1 MANE Select	c.462C>T	p.Ser154Ser	synonymous	Exon 6 of 34	ENSP00000222399.6
LAMB1	ENST00000393560.5	TSL:1	c.462C>T	p.Ser154Ser	synonymous	Exon 6 of 19	ENSP00000377190.1
LAMB1	ENST00000943288.1		c.462C>T	p.Ser154Ser	synonymous	Exon 6 of 34	ENSP00000613347.1

Frequencies

GnomAD3 genomes

AF:

0.112

AC:

16988

AN:

152010

Hom.:

1007

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0788

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.167

Gnomad ASJ

AF:

0.149

Gnomad EAS

AF:

0.0575

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.0673

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.126

Gnomad OTH

AF:

0.135

GnomAD2 exomes

AF:

0.120

AC:

30011

AN:

250258

AF XY:

0.119

show subpopulations

Gnomad AFR exome

AF:

0.0800

Gnomad AMR exome

AF:

0.174

Gnomad ASJ exome

AF:

0.157

Gnomad EAS exome

AF:

0.0536

Gnomad FIN exome

AF:

0.0758

Gnomad NFE exome

AF:

0.128

Gnomad OTH exome

AF:

0.117

GnomAD4 exome

AF:

0.124

AC:

180648

AN:

1455852

Hom.:

11791

Cov.:

AF XY:

0.124

AC XY:

89499

AN XY:

722946

show subpopulations

African (AFR)

AF:

0.0809

AC:

2701

AN:

33378

American (AMR)

AF:

0.169

AC:

7515

AN:

44504

Ashkenazi Jewish (ASJ)

AF:

0.154

AC:

4005

AN:

26058

East Asian (EAS)

AF:

0.0490

AC:

1938

AN:

39552

South Asian (SAS)

AF:

0.114

AC:

9819

AN:

85780

European-Finnish (FIN)

AF:

0.0786

AC:

4195

AN:

53378

Middle Eastern (MID)

AF:

0.140

AC:

803

AN:

5748

European-Non Finnish (NFE)

AF:

0.129

AC:

142472

AN:

1107310

Other (OTH)

AF:

0.120

AC:

7200

AN:

60144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

7519

15038

22557

30076

37595

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5118

10236

15354

20472

25590

<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:

0.112

AC:

16976

AN:

152128

Hom.:

1002

Cov.:

AF XY:

0.111

AC XY:

8246

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.0785

AC:

3259

AN:

41490

American (AMR)

AF:

0.166

AC:

2542

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.149

AC:

517

AN:

3468

East Asian (EAS)

AF:

0.0574

AC:

297

AN:

5170

South Asian (SAS)

AF:

0.112

AC:

541

AN:

4822

European-Finnish (FIN)

AF:

0.0673

AC:

713

AN:

10594

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.126

AC:

8572

AN:

67992

Other (OTH)

AF:

0.133

AC:

280

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

792

1584

2375

3167

3959

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

376

564

752

940

<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:

0.126

Hom.:

2449

Bravo

AF:

0.117

Asia WGS

AF:

0.0570

AC:

199

AN:

3478

EpiCase

AF:

0.131

EpiControl

AF:

0.132

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

6.5

(source)

DANN

Benign

0.69

PhyloP100

-1.5

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over