chr7-108003532-C-T

Variant names:

• chr7-108003532-C-T
• rs4320486
• ENST00000852248.1:c.-87+516G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000852248.1(LAMB1):​c.-87+516G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,086 control chromosomes in the GnomAD database, including 14,677 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 0.43 (14677 hom., cov: 32)
• Consequence: LAMB1 ENST00000852248.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.902
• Publications: 15 publications found

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 Gene-Disease associations (from GenCC):

• cobblestone lissencephaly without muscular or ocular involvement

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, PanelApp Australia, Genomics England PanelApp, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000852248.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMB1	ENST00000852248.1		c.-87+516G>A		intron	N/A	ENSP00000522307.1
	LAMB1	ENST00000943287.1		c.-397G>A		upstream_gene	N/A	ENSP00000613346.1

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65590 AN: 151968 Hom.: 14667 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.442

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.431 AC: 65613 AN: 152086 Hom.: 14677 Cov.: 32 AF XY: 0.431 AC XY: 32034 AN XY: 74350

African (AFR) AF: 0.326 AC: 13527 AN: 41486

American (AMR) AF: 0.491 AC: 7510 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1707 AN: 3472

East Asian (EAS) AF: 0.223 AC: 1149 AN: 5144

South Asian (SAS) AF: 0.402 AC: 1938 AN: 4818

European-Finnish (FIN) AF: 0.455 AC: 4817 AN: 10580

Middle Eastern (MID) AF: 0.458 AC: 132 AN: 288

European-Non Finnish (NFE) AF: 0.491 AC: 33413 AN: 67988

Other (OTH) AF: 0.448 AC: 946 AN: 2110

Alfa AF: 0.467 Hom.: 46318

Bravo AF: 0.429

Asia WGS AF: 0.316 AC: 1097 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.5
DANN	Benign	0.90
PhyloP100		-0.90
PromoterAI		-0.033	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4320486; hg19: chr7-107643977; COSMIC: COSV55969887;