10-76268864-G-A

Position:

• chr10-76268864-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.517-55537G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 151,824 control chromosomes in the GnomAD database, including 24,780 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 0.56 (24780 hom., cov: 31)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0780

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.517-55537G>A		intron_variant		ENST00000611255.5	NP_001292510.1
LRMDA	NM_032024.5	c.433-55537G>A		intron_variant			NP_114413.1
LRMDA	NR_131178.2	n.871-55537G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.517-55537G>A		intron_variant		5	NM_001305581.2	ENSP00000480240	P1
LRMDA	ENST00000372499.5	c.433-55537G>A		intron_variant		1		ENSP00000361577
LRMDA	ENST00000593699.5	n.871-55537G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84235 AN: 151706 Hom.: 24726 Cov.: 31

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.606

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.556 AC: 84342 AN: 151824 Hom.: 24780 Cov.: 31 AF XY: 0.555 AC XY: 41142 AN XY: 74176

Gnomad4 AFR AF: 0.760

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.525

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.607

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.552

Alfa AF: 0.518 Hom.: 2718

Bravo AF: 0.570

Asia WGS AF: 0.585 AC: 2035 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.19
DANN	Benign	0.65

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: rs7087332; hg19: chr10-78028622; COSMIC: COSV65274773; COSMIC: COSV65274773;