NM_001305581.2:c.131+147811G>A

Variant names:

• chr10-75586305-G-A
• rs1594335
• NM_001305581.2:c.131+147811G>A

Variant summary

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

The NM_001305581.2(LRMDA):​c.131+147811G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 145,516 control chromosomes in the GnomAD database, including 30,412 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 0.62 (30412 hom., cov: 24)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.131+147811G>A		intron_variant	Intron 2 of 6	ENST00000611255.5	NP_001292510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.131+147811G>A		intron_variant	Intron 2 of 6	5	NM_001305581.2	ENSP00000480240.1

Frequencies

GnomAD3 genomes AF: 0.618 AC: 89849 AN: 145436 Hom.: 30410 Cov.: 24

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.785

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.676

Gnomad NFE AF: 0.732

Gnomad OTH AF: 0.662

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

GnomAD4 genome AF: 0.618 AC: 89869 AN: 145516 Hom.: 30412 Cov.: 24 AF XY: 0.622 AC XY: 43806 AN XY: 70440

African (AFR) AF: 0.306 AC: 11830 AN: 38632

American (AMR) AF: 0.694 AC: 9998 AN: 14408

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 2532 AN: 3444

East Asian (EAS) AF: 0.850 AC: 4225 AN: 4968

South Asian (SAS) AF: 0.784 AC: 3663 AN: 4670

European-Finnish (FIN) AF: 0.685 AC: 6086 AN: 8886

Middle Eastern (MID) AF: 0.676 AC: 192 AN: 284

European-Non Finnish (NFE) AF: 0.732 AC: 49301 AN: 67314

Other (OTH) AF: 0.665 AC: 1342 AN: 2018

Alfa AF: 0.515 Hom.: 1771

Bravo AF: 0.596

Asia WGS AF: 0.785 AC: 2728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.22
DANN	Benign	0.42
PhyloP100		-1.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1594335; hg19: chr10-77346063;