10-76356341-G-T

Variant names:

• chr10-76356341-G-T
• rs9299535
• NM_001305581.2:c.601+31856G>T

Variant summary

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

The NM_001305581.2(LRMDA):​c.601+31856G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,020 control chromosomes in the GnomAD database, including 9,575 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 0.30 (9575 hom., cov: 32)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.589 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRMDA	NM_001305581.2	MANE Select	c.601+31856G>T		intron	N/A	NP_001292510.1
	LRMDA	NM_032024.5		c.517+31856G>T		intron	N/A	NP_114413.1
	LRMDA	NR_131178.2		n.955+31856G>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRMDA	ENST00000611255.5	TSL:5 MANE Select	c.601+31856G>T		intron	N/A	ENSP00000480240.1
	LRMDA	ENST00000372499.5	TSL:1	c.517+31856G>T		intron	N/A	ENSP00000361577.1
	LRMDA	ENST00000593699.5	TSL:1	n.955+31856G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45541 AN: 151902 Hom.: 9551 Cov.: 32

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.300 AC: 45612 AN: 152020 Hom.: 9575 Cov.: 32 AF XY: 0.303 AC XY: 22475 AN XY: 74288

African (AFR) AF: 0.595 AC: 24657 AN: 41460

American (AMR) AF: 0.188 AC: 2865 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1061 AN: 3468

East Asian (EAS) AF: 0.397 AC: 2039 AN: 5142

South Asian (SAS) AF: 0.286 AC: 1378 AN: 4820

European-Finnish (FIN) AF: 0.239 AC: 2529 AN: 10570

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10311 AN: 67974

Other (OTH) AF: 0.278 AC: 588 AN: 2112

Alfa AF: 0.184 Hom.: 5624

Bravo AF: 0.305

Asia WGS AF: 0.319 AC: 1111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Benign	0.78
PhyloP100		1.1
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: rs9299535; hg19: chr10-78116099;