Variant chr1-183024223-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002293.4(LAMC1):c.418+89G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,301,304 control chromosomes in the GnomAD database, including 11,148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1029 hom., cov: 33)

Exomes 𝑓: 0.13 ( 10119 hom. )

Consequence

LAMC1
NM_002293.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.563

Variant links:

Genes affected

LAMC1 (HGNC:6492): (laminin subunit gamma 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, composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively), have 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 gamma chain isoform laminin, gamma 1. The gamma 1 chain, formerly thought to be a beta chain, contains structural domains similar to beta chains, however, lacks the short alpha region separating domains I and II. The structural organization of this gene also suggested that it had diverged considerably from the beta chain genes. Embryos of transgenic mice in which both alleles of the gamma 1 chain gene were inactivated by homologous recombination, lacked basement membranes, indicating that laminin, gamma 1 chain is necessary for laminin heterotrimer assembly. It has been inferred by analogy with the strikingly similar 3' UTR sequence in mouse laminin gamma 1 cDNA, that multiple polyadenylation sites are utilized in human to generate the 2 different sized mRNAs (5.5 and 7.5 kb) seen on Northern analysis. [provided by RefSeq, Aug 2011]

LAMC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 1-183024223-G-T is Benign according to our data. Variant chr1-183024223-G-T is described in ClinVar as [Benign]. Clinvar id is 1268679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMC1	NM_002293.4 linkuse as main transcript	c.418+89G>T		intron_variant		ENST00000258341.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMC1	ENST00000258341.5 linkuse as main transcript	c.418+89G>T		intron_variant		1	NM_002293.4	P1

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15860

AN:

152190

Hom.:

1025

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0419

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.199

Gnomad ASJ

AF:

0.0855

Gnomad EAS

AF:

0.117

Gnomad SAS

AF:

0.189

Gnomad FIN

AF:

0.104

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.116

Gnomad OTH

AF:

0.110

GnomAD4 exome

AF:

0.129

AC:

148290

AN:

1148998

Hom.:

10119

AF XY:

0.131

AC XY:

73824

AN XY:

563442

show subpopulations

Gnomad4 AFR exome

AF:

0.0352

Gnomad4 AMR exome

AF:

0.260

Gnomad4 ASJ exome

AF:

0.0789

Gnomad4 EAS exome

AF:

0.151

Gnomad4 SAS exome

AF:

0.188

Gnomad4 FIN exome

AF:

0.107

Gnomad4 NFE exome

AF:

0.126

Gnomad4 OTH exome

AF:

0.121

GnomAD4 genome

AF:

0.104

AC:

15875

AN:

152306

Hom.:

1029

Cov.:

AF XY:

0.107

AC XY:

7940

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0418

Gnomad4 AMR

AF:

0.199

Gnomad4 ASJ

AF:

0.0855

Gnomad4 EAS

AF:

0.118

Gnomad4 SAS

AF:

0.189

Gnomad4 FIN

AF:

0.104

Gnomad4 NFE

AF:

0.116

Gnomad4 OTH

AF:

0.112

Alfa

AF:

0.114

Hom.:

143

Bravo

AF:

0.111

Asia WGS

AF:

0.145

AC:

502

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.0

DANN

Benign

0.54

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over