NM_001305581.2:c.517-55537G>A

Variant names:

• chr10-76268864-G-A
• rs7087332
• NM_001305581.2:c.517-55537G>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.517-55537G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 151,824 control chromosomes in the GnomAD database, including 24,780 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 0.56 (24780 hom., cov: 31)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0780
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.517-55537G>A		intron_variant	Intron 5 of 6	ENST00000611255.5	NP_001292510.1
LRMDA	NM_032024.5	c.433-55537G>A		intron_variant	Intron 4 of 5		NP_114413.1
LRMDA	NR_131178.2	n.871-55537G>A		intron_variant	Intron 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.517-55537G>A		intron_variant	Intron 5 of 6	5	NM_001305581.2	ENSP00000480240.1
LRMDA	ENST00000372499.5	c.433-55537G>A		intron_variant	Intron 4 of 5	1		ENSP00000361577.1
LRMDA	ENST00000593699.5	n.871-55537G>A		intron_variant	Intron 6 of 7	1

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84235 AN: 151706 Hom.: 24726 Cov.: 31

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.606

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.556 AC: 84342 AN: 151824 Hom.: 24780 Cov.: 31 AF XY: 0.555 AC XY: 41142 AN XY: 74176

African (AFR) AF: 0.760 AC: 31478 AN: 41396

American (AMR) AF: 0.502 AC: 7650 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1821 AN: 3470

East Asian (EAS) AF: 0.554 AC: 2851 AN: 5144

South Asian (SAS) AF: 0.607 AC: 2915 AN: 4802

European-Finnish (FIN) AF: 0.432 AC: 4547 AN: 10524

Middle Eastern (MID) AF: 0.614 AC: 178 AN: 290

European-Non Finnish (NFE) AF: 0.460 AC: 31221 AN: 67932

Other (OTH) AF: 0.552 AC: 1161 AN: 2104

Alfa AF: 0.610 Hom.: 6708

Bravo AF: 0.570

Asia WGS AF: 0.585 AC: 2035 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.19
DANN	Benign	0.65
PhyloP100		0.078
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: rs7087332; hg19: chr10-78028622; COSMIC: COSV65274773; COSMIC: COSV65274773;