rs7079348

Positions:

• chr10-76312631-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.517-11770C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0362 in 152,020 control chromosomes in the GnomAD database, including 277 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 0.036 (277 hom., cov: 32)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132

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]

LOC112268057 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.517-11770C>T		intron_variant		ENST00000611255.5	NP_001292510.1
LOC112268057	XR_002957050.2	n.393+3374G>A		intron_variant, non_coding_transcript_variant
LRMDA	NM_032024.5	c.433-11770C>T		intron_variant			NP_114413.1
LRMDA	NR_131178.2	n.871-11770C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.517-11770C>T		intron_variant		5	NM_001305581.2	ENSP00000480240	P1
LRMDA	ENST00000372499.5	c.433-11770C>T		intron_variant		1		ENSP00000361577
LRMDA	ENST00000593699.5	n.871-11770C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0362 AC: 5496 AN: 151900 Hom.: 276 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0173

Gnomad ASJ AF: 0.0369

Gnomad EAS AF: 0.00272

Gnomad SAS AF: 0.00623

Gnomad FIN AF: 0.0103

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.00432

Gnomad OTH AF: 0.0306

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

GnomAD4 genome AF: 0.0362 AC: 5507 AN: 152020 Hom.: 277 Cov.: 32 AF XY: 0.0347 AC XY: 2576 AN XY: 74270

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.0173

Gnomad4 ASJ AF: 0.0369

Gnomad4 EAS AF: 0.00273

Gnomad4 SAS AF: 0.00665

Gnomad4 FIN AF: 0.0103

Gnomad4 NFE AF: 0.00431

Gnomad4 OTH AF: 0.0312

Alfa AF: 0.0122 Hom.: 50

Bravo AF: 0.0394

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.94
DANN	Benign	0.71

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: rs7079348; hg19: chr10-78072389;