rs11082762

Variant names:

• chr18-23785889-A-G
• rs11082762
• NM_198129.4:c.1603+1732A>G

Your query was ambiguous. Multiple possible variants found:

• chr18-23785889-A-G
• chr18-23785889-A-T

Variant summary

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

The NM_198129.4(LAMA3):​c.1603+1732A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 152,074 control chromosomes in the GnomAD database, including 19,382 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 0.48 (19382 hom., cov: 32)
• Consequence: LAMA3 NM_198129.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.623

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 = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA3	NM_198129.4	c.1603+1732A>G		intron_variant	Intron 12 of 74	ENST00000313654.14	NP_937762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA3	ENST00000313654.14	c.1603+1732A>G		intron_variant	Intron 12 of 74	1	NM_198129.4	ENSP00000324532.8
LAMA3	ENST00000399516.7	c.1603+1732A>G		intron_variant	Intron 12 of 73	1		ENSP00000382432.2
LAMA3	ENST00000585600.5	n.1603+1732A>G		intron_variant	Intron 12 of 12	1		ENSP00000468316.1

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73174 AN: 151956 Hom.: 19378 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.515

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

GnomAD4 genome AF: 0.481 AC: 73193 AN: 152074 Hom.: 19382 Cov.: 32 AF XY: 0.473 AC XY: 35136 AN XY: 74324

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.659

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.361

Gnomad4 FIN AF: 0.554

Gnomad4 NFE AF: 0.607

Gnomad4 OTH AF: 0.512

Alfa AF: 0.555 Hom.: 11392

Bravo AF: 0.469

Asia WGS AF: 0.264 AC: 921 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	0.55
DANN	Benign	0.55

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: rs11082762; hg19: chr18-21365853;