rs4746308

chr10-75569514-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001305581.2(LRMDA):c.131+131020G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0917 in 152,226 control chromosomes in the GnomAD database, including 869 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 0.092 (869 hom., cov: 33)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRMDA	NM_001305581.2	c.131+131020G>T		intron_variant		ENST00000611255.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRMDA	ENST00000611255.5	c.131+131020G>T		intron_variant		5	NM_001305581.2	P1

Frequencies

GnomAD3 genomes AF: 0.0917 AC: 13944 AN: 152108 Hom.: 865 Cov.: 33

Gnomad AFR AF: 0.0422

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0928

Gnomad ASJ AF: 0.0775

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0950

Gnomad OTH AF: 0.0842

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

GnomAD4 genome AF: 0.0917 AC: 13953 AN: 152226 Hom.: 869 Cov.: 33 AF XY: 0.0946 AC XY: 7036 AN XY: 74410

Gnomad4 AFR AF: 0.0422

Gnomad4 AMR AF: 0.0928

Gnomad4 ASJ AF: 0.0775

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.0950

Gnomad4 OTH AF: 0.0890

Alfa AF: 0.0917 Hom.: 116

Bravo AF: 0.0868

Asia WGS AF: 0.232 AC: 807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
Cadd	Benign	15
Dann	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4746308; hg19: chr10-77329272;