rs717387

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-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/exons	MANE	UniProt
LRMDA	NM_001305581.2	c.516+68953G>A		intron_variant		ENST00000611255.5
LRMDA	NM_032024.5	c.432+68953G>A		intron_variant
LRMDA	NR_131178.2	n.870+68953G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRMDA	ENST00000611255.5	c.516+68953G>A		intron_variant		5	NM_001305581.2	P1
LRMDA	ENST00000372499.5	c.432+68953G>A		intron_variant		1
LRMDA	ENST00000593699.5	n.870+68953G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.762

Gnomad4 AMR AF: 0.555

Gnomad4 ASJ AF: 0.492

Gnomad4 EAS AF: 0.729

Gnomad4 SAS AF: 0.552

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.526

Alfa AF: 0.458 Hom.: 24651

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

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: rs717387; hg19: chr10-77887494;