7-107940901-T-C

Variant names:

• chr7-107940901-T-C
• rs10953555
• NM_002291.3:c.3392-543A>G

Variant summary

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

The NM_002291.3(LAMB1):​c.3392-543A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 152,130 control chromosomes in the GnomAD database, including 31,393 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 0.64 (31393 hom., cov: 33)
• Consequence: LAMB1 NM_002291.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.327
• Publications: 7 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

ENSG00000273055 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002291.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMB1	NM_002291.3	MANE Select	c.3392-543A>G		intron	N/A	NP_002282.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMB1	ENST00000222399.11	TSL:1 MANE Select	c.3392-543A>G		intron	N/A	ENSP00000222399.6
	LAMB1	ENST00000468999.2	TSL:2	n.902A>G		non_coding_transcript_exon	Exon 1 of 11
	LAMB1	ENST00000678310.1		n.902A>G		non_coding_transcript_exon	Exon 1 of 10

Frequencies

GnomAD3 genomes AF: 0.639 AC: 97183 AN: 152012 Hom.: 31366 Cov.: 33

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.644

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

GnomAD4 genome AF: 0.639 AC: 97265 AN: 152130 Hom.: 31393 Cov.: 33 AF XY: 0.644 AC XY: 47858 AN XY: 74360

African (AFR) AF: 0.662 AC: 27471 AN: 41482

American (AMR) AF: 0.643 AC: 9833 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 2305 AN: 3470

East Asian (EAS) AF: 0.850 AC: 4410 AN: 5186

South Asian (SAS) AF: 0.571 AC: 2754 AN: 4820

European-Finnish (FIN) AF: 0.642 AC: 6787 AN: 10570

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.610 AC: 41490 AN: 67992

Other (OTH) AF: 0.644 AC: 1360 AN: 2112

Alfa AF: 0.621 Hom.: 5115

Bravo AF: 0.642

Asia WGS AF: 0.741 AC: 2579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	7.0
DANN	Benign	0.57
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10953555; hg19: chr7-107581346; COSMIC: COSV107294581; COSMIC: COSV107294581;