7-107950293-G-C

Position:

• chr7-107950293-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002291.3(LAMB1):​c.3391+933C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 151,874 control chromosomes in the GnomAD database, including 32,773 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.66 (32773 hom., cov: 32)
• Consequence: LAMB1 NM_002291.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.990

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMB1	NM_002291.3	c.3391+933C>G		intron_variant		ENST00000222399.11	NP_002282.2
LAMB1	XM_047420359.1	c.3391+933C>G		intron_variant			XP_047276315.1
LAMB1	XM_047420360.1	c.3391+933C>G		intron_variant			XP_047276316.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMB1	ENST00000222399.11	c.3391+933C>G		intron_variant		1	NM_002291.3	ENSP00000222399.6

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99603 AN: 151762 Hom.: 32748 Cov.: 32

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.662

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.633

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.656 AC: 99677 AN: 151874 Hom.: 32773 Cov.: 32 AF XY: 0.660 AC XY: 48979 AN XY: 74238

Gnomad4 AFR AF: 0.672

Gnomad4 AMR AF: 0.652

Gnomad4 ASJ AF: 0.692

Gnomad4 EAS AF: 0.839

Gnomad4 SAS AF: 0.636

Gnomad4 FIN AF: 0.683

Gnomad4 NFE AF: 0.630

Gnomad4 OTH AF: 0.634

Alfa AF: 0.539 Hom.: 1514

Bravo AF: 0.651

Asia WGS AF: 0.744 AC: 2587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.80
DANN	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2237696; hg19: chr7-107590738;