rs2072209

Variant names:

• chr7-107951753-A-G
• rs2072209
• NM_002291.3:c.3294+256T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002291.3(LAMB1):​c.3294+256T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.054 in 152,266 control chromosomes in the GnomAD database, including 310 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.054 (310 hom., cov: 32)
• Consequence: LAMB1 NM_002291.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.639
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 7-107951753-A-G is Benign according to our data. Variant chr7-107951753-A-G is described in ClinVar as Benign. ClinVar VariationId is 1239894.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMB1	NM_002291.3	c.3294+256T>C		intron_variant	Intron 23 of 33	ENST00000222399.11	NP_002282.2
LAMB1	XM_047420359.1	c.3294+256T>C		intron_variant	Intron 23 of 27		XP_047276315.1
LAMB1	XM_047420360.1	c.3294+256T>C		intron_variant	Intron 23 of 24		XP_047276316.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMB1	ENST00000222399.11	c.3294+256T>C		intron_variant	Intron 23 of 33	1	NM_002291.3	ENSP00000222399.6

Frequencies

GnomAD3 genomes AF: 0.0541 AC: 8225 AN: 152148 Hom.: 310 Cov.: 32

Gnomad AFR AF: 0.0138

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0873

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.0597

Gnomad FIN AF: 0.0231

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0654

Gnomad OTH AF: 0.0535

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

GnomAD4 genome AF: 0.0540 AC: 8215 AN: 152266 Hom.: 310 Cov.: 32 AF XY: 0.0533 AC XY: 3966 AN XY: 74452

African (AFR) AF: 0.0138 AC: 573 AN: 41560

American (AMR) AF: 0.0871 AC: 1332 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 524 AN: 3470

East Asian (EAS) AF: 0.129 AC: 665 AN: 5166

South Asian (SAS) AF: 0.0597 AC: 288 AN: 4824

European-Finnish (FIN) AF: 0.0231 AC: 245 AN: 10616

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0654 AC: 4449 AN: 68020

Other (OTH) AF: 0.0520 AC: 110 AN: 2114

Alfa AF: 0.0632 Hom.: 1240

Bravo AF: 0.0570

Asia WGS AF: 0.0790 AC: 274 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.36
DANN	Benign	0.74
PhyloP100		-0.64
Mutation Taster		=99/1	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: rs2072209; hg19: chr7-107592198;