rs12041030

Variant names:

• chr1-183097466-A-G
• rs12041030
• NM_002293.4:c.419-5862A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002293.4(LAMC1):​c.419-5862A>G variant causes a intron change. The variant allele was found at a frequency of 0.104 in 152,218 control chromosomes in the GnomAD database, including 1,018 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 0.10 (1018 hom., cov: 32)
• Consequence: LAMC1 NM_002293.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.53
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.191 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.419-5862A>G		intron	N/A	NP_002284.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMC1	ENST00000258341.5	TSL:1 MANE Select	c.419-5862A>G		intron	N/A	ENSP00000258341.3	P11047
	LAMC1	ENST00000920737.1		c.419-5862A>G		intron	N/A	ENSP00000590796.1
	LAMC1	ENST00000920738.1		c.419-5862A>G		intron	N/A	ENSP00000590797.1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15843 AN: 152100 Hom.: 1014 Cov.: 32

Gnomad AFR AF: 0.0420

Gnomad AMI AF: 0.0342

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.0857

Gnomad EAS AF: 0.119

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

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

GnomAD4 genome AF: 0.104 AC: 15857 AN: 152218 Hom.: 1018 Cov.: 32 AF XY: 0.107 AC XY: 7930 AN XY: 74424

African (AFR) AF: 0.0419 AC: 1741 AN: 41550

American (AMR) AF: 0.197 AC: 3018 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0857 AC: 297 AN: 3466

East Asian (EAS) AF: 0.119 AC: 617 AN: 5180

South Asian (SAS) AF: 0.189 AC: 911 AN: 4814

European-Finnish (FIN) AF: 0.104 AC: 1098 AN: 10604

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7897 AN: 68000

Other (OTH) AF: 0.112 AC: 236 AN: 2112

Alfa AF: 0.111 Hom.: 144

Bravo AF: 0.111

Asia WGS AF: 0.146 AC: 505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	17
DANN	Benign	0.83
PhyloP100		4.5
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: rs12041030; hg19: chr1-183066601;