10-75792947-T-C

Position:

• chr10-75792947-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.132-243061T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 152,076 control chromosomes in the GnomAD database, including 47,970 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 0.79 (47970 hom., cov: 31)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.530

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.132-243061T>C		intron_variant		ENST00000611255.5	NP_001292510.1
LRMDA	NM_032024.5	c.47+9925T>C		intron_variant			NP_114413.1
LRMDA	NR_131178.2	n.86-89709T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.132-243061T>C		intron_variant		5	NM_001305581.2	ENSP00000480240	P1
LRMDA	ENST00000372499.5	c.47+9925T>C		intron_variant		1		ENSP00000361577
LRMDA	ENST00000593699.5	n.86-89709T>C		intron_variant, non_coding_transcript_variant		1
LRMDA	ENST00000593817.1	n.92+191616T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.790 AC: 120084 AN: 151958 Hom.: 47912 Cov.: 31

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.959

Gnomad SAS AF: 0.883

Gnomad FIN AF: 0.837

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.722

Gnomad OTH AF: 0.762

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

GnomAD4 genome AF: 0.790 AC: 120202 AN: 152076 Hom.: 47970 Cov.: 31 AF XY: 0.797 AC XY: 59204 AN XY: 74326

Gnomad4 AFR AF: 0.873

Gnomad4 AMR AF: 0.776

Gnomad4 ASJ AF: 0.740

Gnomad4 EAS AF: 0.958

Gnomad4 SAS AF: 0.883

Gnomad4 FIN AF: 0.837

Gnomad4 NFE AF: 0.722

Gnomad4 OTH AF: 0.763

Alfa AF: 0.763 Hom.: 13674

Bravo AF: 0.790

Asia WGS AF: 0.914 AC: 3179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.58

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: rs4746332; hg19: chr10-77552705;