rs17477864

chr1-183144444-A-G

Variant summary

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

The NM_002293.4(LAMC1):c.*1654A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.047 in 152,538 control chromosomes in the GnomAD database, including 265 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 0.047 (265 hom., cov: 31)
  • Exomes 𝑓: 0.014 (0 hom.)
• Consequence: LAMC1 NM_002293.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.693

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 (SAS) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMC1	NM_002293.4	c.*1654A>G		3_prime_UTR_variant	28/28	ENST00000258341.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMC1	ENST00000258341.5	c.*1654A>G		3_prime_UTR_variant	28/28	1	NM_002293.4	P1

Frequencies

GnomAD3 genomes AF: 0.0471 AC: 7159 AN: 151994 Hom.: 263 Cov.: 31

Gnomad AFR AF: 0.0130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0530

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0132

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0478

Gnomad OTH AF: 0.0593

GnomAD4 exome AF: 0.0142 AC: 6 AN: 424 Hom.: 0 Cov.: 0 AF XY: 0.0234 AC XY: 6 AN XY: 256

Gnomad4 FIN exome AF: 0.0120

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.0471 AC: 7170 AN: 152114 Hom.: 265 Cov.: 31 AF XY: 0.0481 AC XY: 3574 AN XY: 74380

Gnomad4 AFR AF: 0.0129

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.0530

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.0132

Gnomad4 NFE AF: 0.0478

Gnomad4 OTH AF: 0.0616

Alfa AF: 0.0534 Hom.: 172

Bravo AF: 0.0549

Asia WGS AF: 0.115 AC: 398 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	0.090
Dann	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs17477864; hg19: chr1-183113579;