rs10509377

chr10-76438991-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+114506G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0224 in 152,240 control chromosomes in the GnomAD database, including 148 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 0.022 (148 hom., cov: 33)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.654

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=-0.7).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRMDA	NM_001305581.2	c.601+114506G>A		intron_variant		ENST00000611255.5
LRMDA	NM_032024.5	c.517+114506G>A		intron_variant
LRMDA	NR_131178.2	n.955+114506G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRMDA	ENST00000611255.5	c.601+114506G>A		intron_variant		5	NM_001305581.2	P1

Frequencies

GnomAD3 genomes AF: 0.0224 AC: 3414 AN: 152122 Hom.: 147 Cov.: 33

Gnomad AFR AF: 0.00367

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.00498

Gnomad FIN AF: 0.0470

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0138

Gnomad OTH AF: 0.0229

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

GnomAD4 genome AF: 0.0224 AC: 3416 AN: 152240 Hom.: 148 Cov.: 33 AF XY: 0.0262 AC XY: 1953 AN XY: 74412

Gnomad4 AFR AF: 0.00366

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00405

Gnomad4 SAS AF: 0.00498

Gnomad4 FIN AF: 0.0470

Gnomad4 NFE AF: 0.0138

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0192 Hom.: 15

Bravo AF: 0.0269

Asia WGS AF: 0.00809 AC: 28 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	8.6
Dann	Benign	0.61

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: rs10509377; hg19: chr10-78198749;