rs1865638

Variant names:

• chr10-76195708-G-A
• rs1865638
• NM_001305581.2:c.517-128693G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001305581.2(LRMDA):​c.517-128693G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,088 control chromosomes in the GnomAD database, including 9,192 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 0.31 (9192 hom., cov: 32)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58
• Publications: 3 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: Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001305581.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRMDA	NM_001305581.2	MANE Select	c.517-128693G>A		intron	N/A	NP_001292510.1	A0A087WWI0
	LRMDA	NM_032024.5		c.433-128693G>A		intron	N/A	NP_114413.1	Q9H2I8
	LRMDA	NR_131178.2		n.871-128693G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRMDA	ENST00000611255.5	TSL:5 MANE Select	c.517-128693G>A		intron	N/A	ENSP00000480240.1	A0A087WWI0
	LRMDA	ENST00000372499.5	TSL:1	c.433-128693G>A		intron	N/A	ENSP00000361577.1	Q9H2I8
	LRMDA	ENST00000593699.5	TSL:1	n.871-128693G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47406 AN: 151970 Hom.: 9160 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.312 AC: 47504 AN: 152088 Hom.: 9192 Cov.: 32 AF XY: 0.316 AC XY: 23530 AN XY: 74360

African (AFR) AF: 0.522 AC: 21649 AN: 41464

American (AMR) AF: 0.315 AC: 4820 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 702 AN: 3472

East Asian (EAS) AF: 0.595 AC: 3071 AN: 5162

South Asian (SAS) AF: 0.343 AC: 1654 AN: 4826

European-Finnish (FIN) AF: 0.190 AC: 2012 AN: 10586

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12655 AN: 67982

Other (OTH) AF: 0.312 AC: 656 AN: 2104

Alfa AF: 0.259 Hom.: 1106

Bravo AF: 0.330

Asia WGS AF: 0.481 AC: 1666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	14
DANN	Benign	0.72
PhyloP100		1.6
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1865638;

hg19: chr10-77955466;