chr1-183140230-AT-A

Position:

• chr1-183140230-AT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000258341.5(LAMC1):​c.4474-173del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.49 (15036 hom., cov: 0)
• Consequence: LAMC1 ENST00000258341.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.67

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-AS1 (HGNC:52645): (LAMC1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-183140230-AT-A is Benign according to our data. Variant chr1-183140230-AT-A is described in ClinVar as [Benign]. Clinvar id is 1248168.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMC1	NM_002293.4	c.4474-173del		intron_variant		ENST00000258341.5	NP_002284.3
LAMC1-AS1	NR_149048.1	n.288+580del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMC1	ENST00000258341.5	c.4474-173del		intron_variant		1	NM_002293.4	ENSP00000258341	P1
LAMC1-AS1	ENST00000457852.3	n.300+580del		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.488 AC: 58709 AN: 120406 Hom.: 15020 Cov.: 0

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.536

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.488 AC: 58733 AN: 120426 Hom.: 15036 Cov.: 0 AF XY: 0.482 AC XY: 27067 AN XY: 56114

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.554

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.593

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.500

Alfa AF: 0.261 Hom.: 609

Asia WGS AF: 0.625 AC: 2095 AN: 3354

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs35690018; hg19: chr1-183109365;