rs11001819

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.602-1743G>A		intron_variant		ENST00000611255.5	NP_001292510.1
LRMDA	NM_032024.5	c.518-1743G>A		intron_variant			NP_114413.1
LRMDA	NR_131178.2	n.956-1743G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.602-1743G>A		intron_variant		5	NM_001305581.2	ENSP00000480240	P1

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

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.397

Alfa AF: 0.453 Hom.: 27245

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs11001819; hg19: chr10-78315224;