rs717387

Variant names:

• chr10-76127736-G-A
• rs717387
• NM_001305581.2:c.516+68953G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-76127736-G-A
• chr10-76127736-G-C

Variant summary

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

The NM_001305581.2(LRMDA):​c.516+68953G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 151,846 control chromosomes in the GnomAD database, including 24,785 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 0.55 (24785 hom., cov: 31)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.311
• Publications: 4 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.516+68953G>A		intron_variant	Intron 5 of 6	ENST00000611255.5	NP_001292510.1
LRMDA	NM_032024.5	c.432+68953G>A		intron_variant	Intron 4 of 5		NP_114413.1
LRMDA	NR_131178.2	n.870+68953G>A		intron_variant	Intron 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.516+68953G>A		intron_variant	Intron 5 of 6	5	NM_001305581.2	ENSP00000480240.1
LRMDA	ENST00000372499.5	c.432+68953G>A		intron_variant	Intron 4 of 5	1		ENSP00000361577.1
LRMDA	ENST00000593699.5	n.870+68953G>A		intron_variant	Intron 6 of 7	1

Frequencies

GnomAD3 genomes AF: 0.554 AC: 83987 AN: 151726 Hom.: 24746 Cov.: 31

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.523

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

GnomAD4 genome AF: 0.554 AC: 84086 AN: 151846 Hom.: 24785 Cov.: 31 AF XY: 0.555 AC XY: 41164 AN XY: 74178

African (AFR) AF: 0.762 AC: 31577 AN: 41452

American (AMR) AF: 0.555 AC: 8472 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1707 AN: 3470

East Asian (EAS) AF: 0.729 AC: 3764 AN: 5164

South Asian (SAS) AF: 0.552 AC: 2659 AN: 4816

European-Finnish (FIN) AF: 0.462 AC: 4835 AN: 10474

Middle Eastern (MID) AF: 0.514 AC: 150 AN: 292

European-Non Finnish (NFE) AF: 0.433 AC: 29384 AN: 67890

Other (OTH) AF: 0.526 AC: 1109 AN: 2110

Alfa AF: 0.477 Hom.: 44814

Bravo AF: 0.570

Asia WGS AF: 0.626 AC: 2175 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.2
DANN	Benign	0.19
PhyloP100		0.31
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: rs717387; hg19: chr10-77887494;