rs25659

chr7-107986325-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.51

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]

ACMG classification

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	UniProt
LAMB1	NM_002291.3	c.462C>T	p.Ser154=	synonymous_variant	6/34	ENST00000222399.11
LAMB1	XM_047420359.1	c.462C>T	p.Ser154=	synonymous_variant	6/28
LAMB1	XM_047420360.1	c.462C>T	p.Ser154=	synonymous_variant	6/25

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16988 AN: 152010 Hom.: 1007 Cov.: 32

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

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.: 32 AF XY: 0.124 AC XY: 89499 AN XY: 722946

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.: 32 AF XY: 0.111 AC XY: 8246 AN XY: 74358

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

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

Other links and lift over

dbSNP: rs25659; hg19: chr7-107626770; COSMIC: COSV55970993;