rs10509377

Variant names:

• chr10-76438991-G-A
• rs10509377
• NM_001305581.2:c.601+114506G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001305581.2(LRMDA):​c.601+114506G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0224 in 152,240 control chromosomes in the GnomAD database, including 148 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 0.022 (148 hom., cov: 33)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.654
• Publications: 2 publications found

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]

LRMDA Gene-Disease associations (from GenCC):

• oculocutaneous albinism type 7

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000230575 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.601+114506G>A		intron_variant	Intron 6 of 6	ENST00000611255.5	NP_001292510.1
LRMDA	NM_032024.5	c.517+114506G>A		intron_variant	Intron 5 of 5		NP_114413.1
LRMDA	NR_131178.2	n.955+114506G>A		intron_variant	Intron 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.601+114506G>A		intron_variant	Intron 6 of 6	5	NM_001305581.2	ENSP00000480240.1

Frequencies

GnomAD3 genomes AF: 0.0224 AC: 3414 AN: 152122 Hom.: 147 Cov.: 33

Gnomad AFR AF: 0.00367

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.00498

Gnomad FIN AF: 0.0470

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0138

Gnomad OTH AF: 0.0229

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

GnomAD4 genome AF: 0.0224 AC: 3416 AN: 152240 Hom.: 148 Cov.: 33 AF XY: 0.0262 AC XY: 1953 AN XY: 74412

African (AFR) AF: 0.00366 AC: 152 AN: 41546

American (AMR) AF: 0.113 AC: 1723 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.00405 AC: 21 AN: 5184

South Asian (SAS) AF: 0.00498 AC: 24 AN: 4820

European-Finnish (FIN) AF: 0.0470 AC: 498 AN: 10586

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0138 AC: 940 AN: 68014

Other (OTH) AF: 0.0227 AC: 48 AN: 2116

Alfa AF: 0.0140 Hom.: 44

Bravo AF: 0.0269

Asia WGS AF: 0.00809 AC: 28 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.6
DANN	Benign	0.61
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

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: rs10509377; hg19: chr10-78198749;