7-107940394-A-G

Position:

• chr7-107940394-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.499

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 (HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
LAMB1	NM_002291.3	c.3392-36T>C		intron_variant		ENST00000222399.11	NP_002282.2
LAMB1	XM_047420359.1	c.3392-36T>C		intron_variant			XP_047276315.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMB1	ENST00000222399.11	c.3392-36T>C		intron_variant		1	NM_002291.3	ENSP00000222399.6

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97335 AN: 151930 Hom.: 31490 Cov.: 32

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

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.: 31 AF XY: 0.614 AC XY: 433071 AN XY: 705348

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.: 32 AF XY: 0.645 AC XY: 47922 AN XY: 74338

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

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	GeneDx	Jun 19, 2018	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	-0.70
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

Other links and lift over

dbSNP: rs2158836; hg19: chr7-107580839;