10-76206739-A-G

Position:

• chr10-76206739-A-G

Variant summary

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

The NM_001305581.2(LRMDA):​c.517-117662A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,124 control chromosomes in the GnomAD database, including 2,519 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 0.15 (2519 hom., cov: 32)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.446

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 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.517-117662A>G		intron_variant		ENST00000611255.5	NP_001292510.1
LRMDA	NM_032024.5	c.433-117662A>G		intron_variant			NP_114413.1
LRMDA	NR_131178.2	n.871-117662A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.517-117662A>G		intron_variant		5	NM_001305581.2	ENSP00000480240.1
LRMDA	ENST00000372499.5	c.433-117662A>G		intron_variant		1		ENSP00000361577.1
LRMDA	ENST00000593699.5	n.871-117662A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23407 AN: 152008 Hom.: 2510 Cov.: 32

Gnomad AFR AF: 0.0433

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.154 AC: 23428 AN: 152124 Hom.: 2519 Cov.: 32 AF XY: 0.162 AC XY: 12008 AN XY: 74344

Gnomad4 AFR AF: 0.0432

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.189

Alfa AF: 0.164 Hom.: 1111

Bravo AF: 0.156

Asia WGS AF: 0.361 AC: 1250 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	3.9
DANN	Benign	0.52

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: rs881631; hg19: chr10-77966497;