1-183124740-T-C

Variant names:

• chr1-183124740-T-C
• rs20557
• NM_002293.4:c.2511T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002293.4(LAMC1):​c.2511T>C​(p.Asn837Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 1,613,798 control chromosomes in the GnomAD database, including 262,271 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (21118 hom., cov: 32)
  • Exomes 𝑓: 0.57 (241153 hom.)
• Consequence: LAMC1 NM_002293.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.74
• Publications: 26 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-183124740-T-C is Benign according to our data. Variant chr1-183124740-T-C is described in ClinVar as Benign. ClinVar VariationId is 1296709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.74 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002293.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMC1	NM_002293.4	MANE Select	c.2511T>C	p.Asn837Asn	synonymous	Exon 14 of 28	NP_002284.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMC1	ENST00000258341.5	TSL:1 MANE Select	c.2511T>C	p.Asn837Asn	synonymous	Exon 14 of 28	ENSP00000258341.3	P11047
	LAMC1	ENST00000920737.1		c.2511T>C	p.Asn837Asn	synonymous	Exon 14 of 29	ENSP00000590796.1
	LAMC1	ENST00000920738.1		c.2502T>C	p.Asn834Asn	synonymous	Exon 14 of 28	ENSP00000590797.1

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78694 AN: 151952 Hom.: 21064 Cov.: 32

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.543

GnomAD2 exomes AF: 0.580 AC: 145878 AN: 251346 AF XY: 0.583

Gnomad AFR exome AF: 0.365

Gnomad AMR exome AF: 0.680

Gnomad ASJ exome AF: 0.492

Gnomad EAS exome AF: 0.621

Gnomad FIN exome AF: 0.596

Gnomad NFE exome AF: 0.559

Gnomad OTH exome AF: 0.566

GnomAD4 exome AF: 0.571 AC: 835260 AN: 1461726 Hom.: 241153 Cov.: 58 AF XY: 0.574 AC XY: 417515 AN XY: 727178

African (AFR) AF: 0.362 AC: 12114 AN: 33480

American (AMR) AF: 0.676 AC: 30224 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 12884 AN: 26136

East Asian (EAS) AF: 0.617 AC: 24507 AN: 39698

South Asian (SAS) AF: 0.653 AC: 56309 AN: 86254

European-Finnish (FIN) AF: 0.593 AC: 31659 AN: 53416

Middle Eastern (MID) AF: 0.541 AC: 3119 AN: 5768

European-Non Finnish (NFE) AF: 0.567 AC: 629990 AN: 1111866

Other (OTH) AF: 0.571 AC: 34454 AN: 60388

GnomAD4 genome AF: 0.518 AC: 78800 AN: 152072 Hom.: 21118 Cov.: 32 AF XY: 0.525 AC XY: 38990 AN XY: 74336

African (AFR) AF: 0.374 AC: 15525 AN: 41480

American (AMR) AF: 0.619 AC: 9459 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1729 AN: 3470

East Asian (EAS) AF: 0.611 AC: 3162 AN: 5176

South Asian (SAS) AF: 0.651 AC: 3136 AN: 4820

European-Finnish (FIN) AF: 0.603 AC: 6375 AN: 10568

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.553 AC: 37589 AN: 67956

Other (OTH) AF: 0.549 AC: 1158 AN: 2108

Alfa AF: 0.543 Hom.: 24454

Bravo AF: 0.511

Asia WGS AF: 0.643 AC: 2235 AN: 3478

EpiCase AF: 0.564

EpiControl AF: 0.560

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.14
DANN	Benign	0.31
PhyloP100		-1.7
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: rs20557; hg19: chr1-183093875; COSMIC: COSV51144070; COSMIC: COSV51144070;