rs25659

Positions:

chr7-107986325-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002291.3(LAMB1):c.462C>T(p.Ser154=) 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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LAMB1	NM_002291.3 linkuse as main transcript	c.462C>T	p.Ser154=	synonymous_variant	6/34	ENST00000222399.11	NP_002282.2
LAMB1	XM_047420359.1 linkuse as main transcript	c.462C>T	p.Ser154=	synonymous_variant	6/28		XP_047276315.1
LAMB1	XM_047420360.1 linkuse as main transcript	c.462C>T	p.Ser154=	synonymous_variant	6/25		XP_047276316.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMB1	ENST00000222399.11 linkuse as main transcript	c.462C>T	p.Ser154=	synonymous_variant	6/34	1	NM_002291.3	ENSP00000222399	P1

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

GnomAD3 exomes

AF:

0.120

AC:

30011

AN:

250258

Hom.:

2035

AF XY:

0.119

AC XY:

16125

AN XY:

135162

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 SAS exome

AF:

0.110

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

Gnomad4 AFR exome

AF:

0.0809

Gnomad4 AMR exome

AF:

0.169

Gnomad4 ASJ exome

AF:

0.154

Gnomad4 EAS exome

AF:

0.0490

Gnomad4 SAS exome

AF:

0.114

Gnomad4 FIN exome

AF:

0.0786

Gnomad4 NFE exome

AF:

0.129

Gnomad4 OTH exome

AF:

0.120

GnomAD4 genome

AF:

0.112

AC:

16976

AN:

152128

Hom.:

1002

Cov.:

AF XY:

0.111

AC XY:

8246

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0785

Gnomad4 AMR

AF:

0.166

Gnomad4 ASJ

AF:

0.149

Gnomad4 EAS

AF:

0.0574

Gnomad4 SAS

AF:

0.112

Gnomad4 FIN

AF:

0.0673

Gnomad4 NFE

AF:

0.126

Gnomad4 OTH

AF:

0.133

Alfa

AF:

0.126

Hom.:

2016

Bravo

AF:

0.117

Asia WGS

AF:

0.0570

AC:

199

AN:

3478

EpiCase

AF:

0.131

EpiControl

AF:

0.132

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 11, 2016

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

BayesDel_noAF

Benign

-0.60

CADD

Benign

6.5

DANN

Benign

0.69

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

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