rs11001819

Variant names:

• chr10-76555466-G-A
• rs11001819
• NM_001305581.2:c.602-1743G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-76555466-G-A
• chr10-76555466-G-C

Variant summary

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

The NM_001305581.2(LRMDA):​c.602-1743G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 151,898 control chromosomes in the GnomAD database, including 13,060 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 (13060 hom., cov: 30)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.587
• Publications: 37 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

ENSG00000269256 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.602-1743G>A		intron_variant	Intron 6 of 6	ENST00000611255.5	NP_001292510.1
LRMDA	NM_032024.5	c.518-1743G>A		intron_variant	Intron 5 of 5		NP_114413.1
LRMDA	NR_131178.2	n.956-1743G>A		intron_variant	Intron 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.602-1743G>A		intron_variant	Intron 6 of 6	5	NM_001305581.2	ENSP00000480240.1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61204 AN: 151780 Hom.: 13054 Cov.: 30

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.403 AC: 61236 AN: 151898 Hom.: 13060 Cov.: 30 AF XY: 0.399 AC XY: 29580 AN XY: 74208

African (AFR) AF: 0.327 AC: 13540 AN: 41422

American (AMR) AF: 0.314 AC: 4788 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1488 AN: 3470

East Asian (EAS) AF: 0.144 AC: 744 AN: 5160

South Asian (SAS) AF: 0.391 AC: 1883 AN: 4810

European-Finnish (FIN) AF: 0.438 AC: 4605 AN: 10524

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32773 AN: 67932

Other (OTH) AF: 0.397 AC: 835 AN: 2104

Alfa AF: 0.447 Hom.: 56063

Bravo AF: 0.386

Asia WGS AF: 0.273 AC: 949 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.77
PhyloP100		0.59
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: rs11001819; hg19: chr10-78315224;