10-76206739-A-G

Variant names:

• chr10-76206739-A-G
• rs881631
• NM_001305581.2:c.517-117662A>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.517-117662A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,124 control chromosomes in the GnomAD database, including 2,519 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 0.15 (2519 hom., cov: 32)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.446
• Publications: 6 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.517-117662A>G		intron_variant	Intron 5 of 6	ENST00000611255.5	NP_001292510.1
LRMDA	NM_032024.5	c.433-117662A>G		intron_variant	Intron 4 of 5		NP_114413.1
LRMDA	NR_131178.2	n.871-117662A>G		intron_variant	Intron 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.517-117662A>G		intron_variant	Intron 5 of 6	5	NM_001305581.2	ENSP00000480240.1
LRMDA	ENST00000372499.5	c.433-117662A>G		intron_variant	Intron 4 of 5	1		ENSP00000361577.1
LRMDA	ENST00000593699.5	n.871-117662A>G		intron_variant	Intron 6 of 7	1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23407 AN: 152008 Hom.: 2510 Cov.: 32

Gnomad AFR AF: 0.0433

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.154 AC: 23428 AN: 152124 Hom.: 2519 Cov.: 32 AF XY: 0.162 AC XY: 12008 AN XY: 74344

African (AFR) AF: 0.0432 AC: 1794 AN: 41550

American (AMR) AF: 0.247 AC: 3777 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 472 AN: 3466

East Asian (EAS) AF: 0.524 AC: 2689 AN: 5128

South Asian (SAS) AF: 0.256 AC: 1233 AN: 4824

European-Finnish (FIN) AF: 0.156 AC: 1649 AN: 10586

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11198 AN: 67966

Other (OTH) AF: 0.189 AC: 399 AN: 2110

Alfa AF: 0.163 Hom.: 1229

Bravo AF: 0.156

Asia WGS AF: 0.361 AC: 1250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.9
DANN	Benign	0.52
PhyloP100		0.45
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: rs881631; hg19: chr10-77966497;