rs10509370

chr10-76356028-T-C

Variant summary

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

The NM_001305581.2(LRMDA):c.601+31543T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,078 control chromosomes in the GnomAD database, including 5,913 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 0.25 (5913 hom., cov: 32)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.799

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRMDA	NM_001305581.2	c.601+31543T>C		intron_variant		ENST00000611255.5
LRMDA	NM_032024.5	c.517+31543T>C		intron_variant
LRMDA	NR_131178.2	n.955+31543T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRMDA	ENST00000611255.5	c.601+31543T>C		intron_variant		5	NM_001305581.2	P1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38535 AN: 151960 Hom.: 5914 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.0493

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.253 AC: 38526 AN: 152078 Hom.: 5913 Cov.: 32 AF XY: 0.249 AC XY: 18480 AN XY: 74326

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.0490

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.256

Alfa AF: 0.319 Hom.: 1637

Bravo AF: 0.239

Asia WGS AF: 0.0730 AC: 255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.1
Dann	Benign	0.73

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: rs10509370; hg19: chr10-78115786;