rs12249859

Variant names:

• chr10-76211434-A-C
• rs12249859
• NM_001305581.2:c.517-112967A>C

Your query was ambiguous. Multiple possible variants found:

• chr10-76211434-A-C
• chr10-76211434-A-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.517-112967A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,216 control chromosomes in the GnomAD database, including 6,988 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 0.28 (6988 hom., cov: 33)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.517-112967A>C		intron_variant	Intron 5 of 6	ENST00000611255.5	NP_001292510.1
LRMDA	NM_032024.5	c.433-112967A>C		intron_variant	Intron 4 of 5		NP_114413.1
LRMDA	NR_131178.2	n.871-112967A>C		intron_variant	Intron 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.517-112967A>C		intron_variant	Intron 5 of 6	5	NM_001305581.2	ENSP00000480240.1
LRMDA	ENST00000372499.5	c.433-112967A>C		intron_variant	Intron 4 of 5	1		ENSP00000361577.1
LRMDA	ENST00000593699.5	n.871-112967A>C		intron_variant	Intron 6 of 7	1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42615 AN: 152098 Hom.: 6962 Cov.: 33

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.281 AC: 42702 AN: 152216 Hom.: 6988 Cov.: 33 AF XY: 0.286 AC XY: 21289 AN XY: 74428

African (AFR) AF: 0.416 AC: 17242 AN: 41490

American (AMR) AF: 0.302 AC: 4627 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 607 AN: 3472

East Asian (EAS) AF: 0.602 AC: 3117 AN: 5182

South Asian (SAS) AF: 0.331 AC: 1597 AN: 4822

European-Finnish (FIN) AF: 0.190 AC: 2021 AN: 10610

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12615 AN: 68020

Other (OTH) AF: 0.282 AC: 595 AN: 2112

Alfa AF: 0.237 Hom.: 856

Bravo AF: 0.292

Asia WGS AF: 0.477 AC: 1652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.70
PhyloP100		0.0080
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: rs12249859; hg19: chr10-77971192;