rs12073936

Variant names:

• chr1-183092755-T-G
• rs12073936
• NM_002293.4:c.419-10573T>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002293.4(LAMC1):​c.419-10573T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0818 in 152,218 control chromosomes in the GnomAD database, including 895 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.082 (895 hom., cov: 32)
• Consequence: LAMC1 NM_002293.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.531

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMC1	NM_002293.4	c.419-10573T>G		intron_variant	Intron 1 of 27	ENST00000258341.5	NP_002284.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMC1	ENST00000258341.5	c.419-10573T>G		intron_variant	Intron 1 of 27	1	NM_002293.4	ENSP00000258341.3

Frequencies

GnomAD3 genomes AF: 0.0819 AC: 12458 AN: 152100 Hom.: 893 Cov.: 32

Gnomad AFR AF: 0.0199

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0721

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.0925

Gnomad FIN AF: 0.0906

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0874

Gnomad OTH AF: 0.0869

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

GnomAD4 genome AF: 0.0818 AC: 12459 AN: 152218 Hom.: 895 Cov.: 32 AF XY: 0.0838 AC XY: 6239 AN XY: 74430

Gnomad4 AFR AF: 0.0198

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0721

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.0925

Gnomad4 FIN AF: 0.0906

Gnomad4 NFE AF: 0.0874

Gnomad4 OTH AF: 0.0865

Alfa AF: 0.0860 Hom.: 710

Bravo AF: 0.0826

Asia WGS AF: 0.244 AC: 848 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.8
DANN	Benign	0.61

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

Other links and lift over

dbSNP: rs12073936; hg19: chr1-183061890;