rs2701039

chr7-107983097-A-Gchr7-107983097-A-T

Variant summary

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

The NM_002291.3(LAMB1):c.677-2286T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 152,082 control chromosomes in the GnomAD database, including 27,829 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 0.60 (27829 hom., cov: 32)
• Consequence: LAMB1 NM_002291.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMB1	NM_002291.3	c.677-2286T>C		intron_variant		ENST00000222399.11
LAMB1	XM_047420359.1	c.677-2286T>C		intron_variant
LAMB1	XM_047420360.1	c.677-2286T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMB1	ENST00000222399.11	c.677-2286T>C		intron_variant		1	NM_002291.3	P1

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90806 AN: 151964 Hom.: 27787 Cov.: 32

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.598 AC: 90904 AN: 152082 Hom.: 27829 Cov.: 32 AF XY: 0.594 AC XY: 44141 AN XY: 74338

Gnomad4 AFR AF: 0.709

Gnomad4 AMR AF: 0.610

Gnomad4 ASJ AF: 0.675

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.513

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.600

Alfa AF: 0.578 Hom.: 33429

Bravo AF: 0.611

Asia WGS AF: 0.409 AC: 1424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.027
Dann	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2701039; hg19: chr7-107623542;