10-76339557-C-T

Position:

• chr10-76339557-C-T

Variant summary

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

The NM_001305581.2(LRMDA):​c.601+15072C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 151,950 control chromosomes in the GnomAD database, including 62,638 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 0.90 (62638 hom., cov: 32)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130

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=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRMDA	NM_001305581.2	c.601+15072C>T		intron_variant		ENST00000611255.5
LRMDA	NM_032024.5	c.517+15072C>T		intron_variant
LRMDA	NR_131178.2	n.955+15072C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRMDA	ENST00000611255.5	c.601+15072C>T		intron_variant		5	NM_001305581.2	P1

Frequencies

GnomAD3 genomes AF: 0.903 AC: 137179 AN: 151832 Hom.: 62610 Cov.: 32

Gnomad AFR AF: 0.912

Gnomad AMI AF: 0.989

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.890

Gnomad MID AF: 0.948

Gnomad NFE AF: 0.956

Gnomad OTH AF: 0.903

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

GnomAD4 genome AF: 0.903 AC: 137256 AN: 151950 Hom.: 62638 Cov.: 32 AF XY: 0.894 AC XY: 66437 AN XY: 74300

Gnomad4 AFR AF: 0.912

Gnomad4 AMR AF: 0.828

Gnomad4 ASJ AF: 0.916

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.700

Gnomad4 FIN AF: 0.890

Gnomad4 NFE AF: 0.956

Gnomad4 OTH AF: 0.902

Alfa AF: 0.931 Hom.: 7707

Bravo AF: 0.897

Asia WGS AF: 0.618 AC: 2118 AN: 3424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.22

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: rs2395373; hg19: chr10-78099315;