7-107940394-A-G

Variant names:

• chr7-107940394-A-G
• rs2158836
• NM_002291.3:c.3392-36T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002291.3(LAMB1):​c.3392-36T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 1,580,378 control chromosomes in the GnomAD database, including 304,279 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (31514 hom., cov: 32)
  • Exomes 𝑓: 0.62 (272765 hom.)
• Consequence: LAMB1 NM_002291.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.499
• Publications: 36 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 7-107940394-A-G is Benign according to our data. Variant chr7-107940394-A-G is described in CliVar as Benign. Clinvar id is 682979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-107940394-A-G is described in CliVar as Benign. Clinvar id is 682979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-107940394-A-G is described in CliVar as Benign. Clinvar id is 682979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-107940394-A-G is described in CliVar as Benign. Clinvar id is 682979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-107940394-A-G is described in CliVar as Benign. Clinvar id is 682979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-107940394-A-G is described in CliVar as Benign. Clinvar id is 682979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-107940394-A-G is described in CliVar as Benign. Clinvar id is 682979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-107940394-A-G is described in CliVar as Benign. Clinvar id is 682979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-107940394-A-G is described in CliVar as Benign. Clinvar id is 682979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-107940394-A-G is described in CliVar as Benign. Clinvar id is 682979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMB1	NM_002291.3	c.3392-36T>C		intron_variant	Intron 24 of 33	ENST00000222399.11	NP_002282.2
LAMB1	XM_047420359.1	c.3392-36T>C		intron_variant	Intron 24 of 27		XP_047276315.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMB1	ENST00000222399.11	c.3392-36T>C		intron_variant	Intron 24 of 33	1	NM_002291.3	ENSP00000222399.6

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97335 AN: 151930 Hom.: 31490 Cov.: 32

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.644

GnomAD2 exomes AF: 0.629 AC: 148130 AN: 235604 AF XY: 0.625

Gnomad AFR exome AF: 0.658

Gnomad AMR exome AF: 0.595

Gnomad ASJ exome AF: 0.673

Gnomad EAS exome AF: 0.848

Gnomad FIN exome AF: 0.634

Gnomad NFE exome AF: 0.609

Gnomad OTH exome AF: 0.639

GnomAD4 exome AF: 0.615 AC: 878774 AN: 1428330 Hom.: 272765 Cov.: 31 AF XY: 0.614 AC XY: 433071 AN XY: 705348

African (AFR) AF: 0.670 AC: 22051 AN: 32894

American (AMR) AF: 0.607 AC: 26190 AN: 43170

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 16397 AN: 24674

East Asian (EAS) AF: 0.865 AC: 33739 AN: 39016

South Asian (SAS) AF: 0.559 AC: 46861 AN: 83810

European-Finnish (FIN) AF: 0.629 AC: 32922 AN: 52346

Middle Eastern (MID) AF: 0.625 AC: 3121 AN: 4996

European-Non Finnish (NFE) AF: 0.607 AC: 660367 AN: 1088618

Other (OTH) AF: 0.631 AC: 37126 AN: 58806

GnomAD4 genome AF: 0.641 AC: 97414 AN: 152048 Hom.: 31514 Cov.: 32 AF XY: 0.645 AC XY: 47922 AN XY: 74338

African (AFR) AF: 0.663 AC: 27483 AN: 41460

American (AMR) AF: 0.644 AC: 9840 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 2307 AN: 3472

East Asian (EAS) AF: 0.852 AC: 4410 AN: 5174

South Asian (SAS) AF: 0.574 AC: 2765 AN: 4814

European-Finnish (FIN) AF: 0.643 AC: 6803 AN: 10578

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

European-Non Finnish (NFE) AF: 0.612 AC: 41591 AN: 67964

Other (OTH) AF: 0.644 AC: 1361 AN: 2112

Alfa AF: 0.623 Hom.: 142407

Bravo AF: 0.643

Asia WGS AF: 0.743 AC: 2584 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	3.9
DANN	Benign	0.85
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2158836; hg19: chr7-107580839;