Variant chr1-183023890-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002293.4(LAMC1):c.174C>T(p.Ala58=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 1,612,232 control chromosomes in the GnomAD database, including 244,117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 19600 hom., cov: 33)

Exomes 𝑓: 0.55 ( 224517 hom. )

Consequence

LAMC1
NM_002293.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.296

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 1-183023890-C-T is Benign according to our data. Variant chr1-183023890-C-T is described in ClinVar as [Benign]. Clinvar id is 1179935.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.296 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.619 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.174C>T	p.Ala58=	synonymous_variant	1/28	ENST00000258341.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMC1	ENST00000258341.5 linkuse as main transcript	c.174C>T	p.Ala58=	synonymous_variant	1/28	1	NM_002293.4	P1

Frequencies

GnomAD3 genomes

AF:

0.498

AC:

75664

AN:

151868

Hom.:

19550

Cov.:

show subpopulations

Gnomad AFR

AF:

0.357

Gnomad AMI

AF:

0.551

Gnomad AMR

AF:

0.597

Gnomad ASJ

AF:

0.471

Gnomad EAS

AF:

0.612

Gnomad SAS

AF:

0.635

Gnomad FIN

AF:

0.594

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.529

Gnomad OTH

AF:

0.511

GnomAD3 exomes

AF:

0.562

AC:

138332

AN:

246000

Hom.:

39888

AF XY:

0.565

AC XY:

75571

AN XY:

133852

show subpopulations

Gnomad AFR exome

AF:

0.346

Gnomad AMR exome

AF:

0.669

Gnomad ASJ exome

AF:

0.464

Gnomad EAS exome

AF:

0.623

Gnomad SAS exome

AF:

0.644

Gnomad FIN exome

AF:

0.584

Gnomad NFE exome

AF:

0.534

Gnomad OTH exome

AF:

0.538

GnomAD4 exome

AF:

0.551

AC:

804782

AN:

1460246

Hom.:

224517

Cov.:

AF XY:

0.554

AC XY:

402166

AN XY:

726368

show subpopulations

Gnomad4 AFR exome

AF:

0.346

Gnomad4 AMR exome

AF:

0.662

Gnomad4 ASJ exome

AF:

0.464

Gnomad4 EAS exome

AF:

0.619

Gnomad4 SAS exome

AF:

0.638

Gnomad4 FIN exome

AF:

0.579

Gnomad4 NFE exome

AF:

0.545

Gnomad4 OTH exome

AF:

0.548

GnomAD4 genome

AF:

0.498

AC:

75765

AN:

151986

Hom.:

19600

Cov.:

AF XY:

0.506

AC XY:

37591

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.358

Gnomad4 AMR

AF:

0.597

Gnomad4 ASJ

AF:

0.471

Gnomad4 EAS

AF:

0.612

Gnomad4 SAS

AF:

0.637

Gnomad4 FIN

AF:

0.594

Gnomad4 NFE

AF:

0.529

Gnomad4 OTH

AF:

0.518

Alfa

AF:

0.508

Hom.:

11719

Bravo

AF:

0.491

Asia WGS

AF:

0.638

AC:

2218

AN:

3478

EpiCase

AF:

0.536

EpiControl

AF:

0.532

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 04, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.96

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