10-75793428-A-G

Variant names:

• chr10-75793428-A-G
• rs10509361
• NM_001305581.2:c.132-242580A>G

Variant summary

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

The NM_001305581.2(LRMDA):​c.132-242580A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,006 control chromosomes in the GnomAD database, including 13,775 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 0.40 (13775 hom., cov: 32)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• 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: 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=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.132-242580A>G		intron_variant	Intron 2 of 6	ENST00000611255.5	NP_001292510.1
LRMDA	NM_032024.5	c.47+10406A>G		intron_variant	Intron 1 of 5		NP_114413.1
LRMDA	NR_131178.2	n.86-89228A>G		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.132-242580A>G		intron_variant	Intron 2 of 6	5	NM_001305581.2	ENSP00000480240.1
LRMDA	ENST00000372499.5	c.47+10406A>G		intron_variant	Intron 1 of 5	1		ENSP00000361577.1
LRMDA	ENST00000593699.5	n.86-89228A>G		intron_variant	Intron 1 of 7	1
LRMDA	ENST00000593817.1	n.92+192097A>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60605 AN: 151886 Hom.: 13765 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.399 AC: 60635 AN: 152006 Hom.: 13775 Cov.: 32 AF XY: 0.402 AC XY: 29892 AN XY: 74302

African (AFR) AF: 0.178 AC: 7364 AN: 41452

American (AMR) AF: 0.411 AC: 6284 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1224 AN: 3468

East Asian (EAS) AF: 0.341 AC: 1765 AN: 5172

South Asian (SAS) AF: 0.522 AC: 2505 AN: 4796

European-Finnish (FIN) AF: 0.527 AC: 5578 AN: 10576

Middle Eastern (MID) AF: 0.325 AC: 95 AN: 292

European-Non Finnish (NFE) AF: 0.507 AC: 34469 AN: 67950

Other (OTH) AF: 0.390 AC: 823 AN: 2110

Alfa AF: 0.466 Hom.: 12794

Bravo AF: 0.378

Asia WGS AF: 0.411 AC: 1430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	16
DANN	Benign	0.70
PhyloP100		1.2
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: rs10509361; hg19: chr10-77553186;