1-183140230-AT-A

Variant names:

• chr1-183140230-AT-A
• rs35690018
• NM_002293.4:c.4474-173delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002293.4(LAMC1):​c.4474-173delT 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 NM_002293.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.67
• Publications: 1 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]

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.4474-173delT		intron	N/A	NP_002284.3
	LAMC1-AS1	NR_149048.1		n.288+580delA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMC1	ENST00000258341.5	TSL:1 MANE Select	c.4474-173delT		intron	N/A	ENSP00000258341.3	P11047
	LAMC1	ENST00000920737.1		c.4525-173delT		intron	N/A	ENSP00000590796.1
	LAMC1	ENST00000920738.1		c.4465-173delT		intron	N/A	ENSP00000590797.1

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

African (AFR) AF: 0.368 AC: 11938 AN: 32422

American (AMR) AF: 0.554 AC: 5745 AN: 10378

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1556 AN: 3128

East Asian (EAS) AF: 0.569 AC: 2256 AN: 3968

South Asian (SAS) AF: 0.593 AC: 1958 AN: 3302

European-Finnish (FIN) AF: 0.447 AC: 2087 AN: 4664

Middle Eastern (MID) AF: 0.543 AC: 125 AN: 230

European-Non Finnish (NFE) AF: 0.531 AC: 31862 AN: 59962

Other (OTH) AF: 0.500 AC: 790 AN: 1580

Alfa AF: 0.261 Hom.: 609

Asia WGS AF: 0.625 AC: 2095 AN: 3354

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-3.7
Mutation Taster		=97/3	polymorphism

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: rs35690018; hg19: chr1-183109365;