rs12373237

chr18-23845972-G-Achr18-23845972-G-T

Variant summary

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

The NM_198129.4(LAMA3):c.3720-325G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 151,980 control chromosomes in the GnomAD database, including 18,964 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 0.47 (18964 hom., cov: 32)
• Consequence: LAMA3 NM_198129.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500

Genes affected

LAMA3 (HGNC:6483): (laminin subunit alpha 3) The protein encoded by this gene belongs to the laminin family of secreted molecules. Laminins are heterotrimeric molecules that consist of alpha, beta, and gamma subunits that assemble through a coiled-coil domain. Laminins are essential for formation and function of the basement membrane and have additional functions in regulating cell migration and mechanical signal transduction. This gene encodes an alpha subunit and is responsive to several epithelial-mesenchymal regulators including keratinocyte growth factor, epidermal growth factor and insulin-like growth factor. Mutations in this gene have been identified as the cause of Herlitz type junctional epidermolysis bullosa and laryngoonychocutaneous syndrome. Alternative splicing and alternative promoter usage result in multiple transcript variants. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMA3	NM_198129.4	c.3720-325G>A		intron_variant		ENST00000313654.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMA3	ENST00000313654.14	c.3720-325G>A		intron_variant		1	NM_198129.4	P1
LAMA3	ENST00000399516.7	c.3720-325G>A		intron_variant		1
LAMA3	ENST00000649721.1	c.612-325G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71052 AN: 151862 Hom.: 18966 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.468 AC: 71058 AN: 151980 Hom.: 18964 Cov.: 32 AF XY: 0.459 AC XY: 34132 AN XY: 74288

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.664

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.548

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.502

Alfa AF: 0.531 Hom.: 3924

Bravo AF: 0.451

Asia WGS AF: 0.274 AC: 953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.68
Dann	Benign	0.66

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: rs12373237; hg19: chr18-21425936;