7-107940394-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002291.3(LAMB1):c.3392-36T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 1,580,378 control chromosomes in the GnomAD database, including 304,279 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 31514 hom., cov: 32)

Exomes 𝑓: 0.62 ( 272765 hom. )

Consequence

LAMB1
NM_002291.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.499

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 7-107940394-A-G is Benign according to our data. Variant chr7-107940394-A-G is described in ClinVar as [Benign]. Clinvar id is 682979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMB1	NM_002291.3 link	c.3392-36T>C		intron_variant	Intron 24 of 33	ENST00000222399.11	NP_002282.2	P07942Q8TAS6
LAMB1	XM_047420359.1 link	c.3392-36T>C		intron_variant	Intron 24 of 27		XP_047276315.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMB1	ENST00000222399.11 link	c.3392-36T>C		intron_variant	Intron 24 of 33	1	NM_002291.3	ENSP00000222399.6		P07942

Frequencies

GnomAD3 genomes

AF:

0.641

AC:

97335

AN:

151930

Hom.:

31490

Cov.:

show subpopulations

Gnomad AFR

AF:

0.663

Gnomad AMI

AF:

0.719

Gnomad AMR

AF:

0.644

Gnomad ASJ

AF:

0.664

Gnomad EAS

AF:

0.853

Gnomad SAS

AF:

0.575

Gnomad FIN

AF:

0.643

Gnomad MID

AF:

0.696

Gnomad NFE

AF:

0.612

Gnomad OTH

AF:

0.644

GnomAD3 exomes

AF:

0.629

AC:

148130

AN:

235604

Hom.:

46899

AF XY:

0.625

AC XY:

79383

AN XY:

126968

show subpopulations

Gnomad AFR exome

AF:

0.658

Gnomad AMR exome

AF:

0.595

Gnomad ASJ exome

AF:

0.673

Gnomad EAS exome

AF:

0.848

Gnomad SAS exome

AF:

0.564

Gnomad FIN exome

AF:

0.634

Gnomad NFE exome

AF:

0.609

Gnomad OTH exome

AF:

0.639

GnomAD4 exome

AF:

0.615

AC:

878774

AN:

1428330

Hom.:

272765

Cov.:

AF XY:

0.614

AC XY:

433071

AN XY:

705348

show subpopulations

Gnomad4 AFR exome

AF:

0.670

Gnomad4 AMR exome

AF:

0.607

Gnomad4 ASJ exome

AF:

0.665

Gnomad4 EAS exome

AF:

0.865

Gnomad4 SAS exome

AF:

0.559

Gnomad4 FIN exome

AF:

0.629

Gnomad4 NFE exome

AF:

0.607

Gnomad4 OTH exome

AF:

0.631

GnomAD4 genome

AF:

0.641

AC:

97414

AN:

152048

Hom.:

31514

Cov.:

AF XY:

0.645

AC XY:

47922

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.663

Gnomad4 AMR

AF:

0.644

Gnomad4 ASJ

AF:

0.664

Gnomad4 EAS

AF:

0.852

Gnomad4 SAS

AF:

0.574

Gnomad4 FIN

AF:

0.643

Gnomad4 NFE

AF:

0.612

Gnomad4 OTH

AF:

0.644

Alfa

AF:

0.623

Hom.:

70057

Bravo

AF:

0.643

Asia WGS

AF:

0.743

AC:

2584

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 19, 2018

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

3.9

DANN

Benign

0.85

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over