rs7894847

Positions:

• chr10-75597269-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.131+158775C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,136 control chromosomes in the GnomAD database, including 5,877 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 0.16 (5877 hom., cov: 31)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.546

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]

ENSG00000286715 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.131+158775C>T		intron_variant		ENST00000611255.5	NP_001292510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.131+158775C>T		intron_variant		5	NM_001305581.2	ENSP00000480240.1
ENSG00000286715	ENST00000670381.1	n.65+4561C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23561 AN: 152018 Hom.: 5845 Cov.: 31

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0712

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00435

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.00632

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.155 AC: 23638 AN: 152136 Hom.: 5877 Cov.: 31 AF XY: 0.149 AC XY: 11082 AN XY: 74392

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.0710

Gnomad4 ASJ AF: 0.0366

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00415

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00632

Gnomad4 OTH AF: 0.130

Alfa AF: 0.0959 Hom.: 438

Bravo AF: 0.178

Asia WGS AF: 0.0340 AC: 120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.2
DANN	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7894847; hg19: chr10-77357027;