rs10509374

chr10-76407893-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001305581.2(LRMDA):c.601+83408G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.041 in 152,250 control chromosomes in the GnomAD database, including 244 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 0.041 (244 hom., cov: 32)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRMDA	NM_001305581.2	c.601+83408G>A		intron_variant		ENST00000611255.5
LRMDA	NM_032024.5	c.517+83408G>A		intron_variant
LRMDA	NR_131178.2	n.955+83408G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRMDA	ENST00000611255.5	c.601+83408G>A		intron_variant		5	NM_001305581.2	P1

Frequencies

GnomAD3 genomes AF: 0.0410 AC: 6233 AN: 152132 Hom.: 245 Cov.: 32

Gnomad AFR AF: 0.0575

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.0524

Gnomad SAS AF: 0.0163

Gnomad FIN AF: 0.0473

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0144

Gnomad OTH AF: 0.0373

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

GnomAD4 genome AF: 0.0410 AC: 6239 AN: 152250 Hom.: 244 Cov.: 32 AF XY: 0.0449 AC XY: 3340 AN XY: 74438

Gnomad4 AFR AF: 0.0575

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.0110

Gnomad4 EAS AF: 0.0527

Gnomad4 SAS AF: 0.0163

Gnomad4 FIN AF: 0.0473

Gnomad4 NFE AF: 0.0144

Gnomad4 OTH AF: 0.0369

Alfa AF: 0.0310 Hom.: 23

Bravo AF: 0.0486

Asia WGS AF: 0.0360 AC: 125 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.3
Dann	Benign	0.53

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: rs10509374; hg19: chr10-78167651;