rs1594335

chr10-75586305-G-Achr10-75586305-G-Cchr10-75586305-G-T

Variant summary

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

The NM_001305581.2(LRMDA):c.131+147811G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 145,516 control chromosomes in the GnomAD database, including 30,412 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 0.62 (30412 hom., cov: 24)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

Genes affected

LRMDA (HGNC:23405): (leucine rich melanocyte differentiation associated) This gene encodes a leucine-rich repeat protein. The encoded protein is thought to play a role in melanocyte differentiation. Mutations in this gene have been associated with autosomal recessive oculocutaneous albinism 7 (OCA7). Alternatively spliced transcript variants have been identified. [provided by RefSeq, Mar 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRMDA	NM_001305581.2	c.131+147811G>A		intron_variant		ENST00000611255.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRMDA	ENST00000611255.5	c.131+147811G>A		intron_variant		5	NM_001305581.2	P1

Frequencies

GnomAD3 genomes AF: 0.618 AC: 89849 AN: 145436 Hom.: 30410 Cov.: 24

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.785

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.676

Gnomad NFE AF: 0.732

Gnomad OTH AF: 0.662

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

GnomAD4 genome AF: 0.618 AC: 89869 AN: 145516 Hom.: 30412 Cov.: 24 AF XY: 0.622 AC XY: 43806 AN XY: 70440

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.694

Gnomad4 ASJ AF: 0.735

Gnomad4 EAS AF: 0.850

Gnomad4 SAS AF: 0.784

Gnomad4 FIN AF: 0.685

Gnomad4 NFE AF: 0.732

Gnomad4 OTH AF: 0.665

Alfa AF: 0.533 Hom.: 1732

Bravo AF: 0.596

Asia WGS AF: 0.785 AC: 2728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.22
Dann	Benign	0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1594335; hg19: chr10-77346063;