rs7079348

Variant names:

• chr10-76312631-C-T
• rs7079348
• NM_001305581.2:c.517-11770C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

LRMDA Gene-Disease associations (from GenCC):

• oculocutaneous albinism type 7

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet

LOC112268057 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.517-11770C>T		intron_variant	Intron 5 of 6	ENST00000611255.5	NP_001292510.1
LRMDA	NM_032024.5	c.433-11770C>T		intron_variant	Intron 4 of 5		NP_114413.1
LRMDA	NR_131178.2	n.871-11770C>T		intron_variant	Intron 6 of 7
LOC112268057	XR_002957050.2	n.393+3374G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.517-11770C>T		intron_variant	Intron 5 of 6	5	NM_001305581.2	ENSP00000480240.1
LRMDA	ENST00000372499.5	c.433-11770C>T		intron_variant	Intron 4 of 5	1		ENSP00000361577.1
LRMDA	ENST00000593699.5	n.871-11770C>T		intron_variant	Intron 6 of 7	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

African (AFR) AF: 0.111 AC: 4589 AN: 41434

American (AMR) AF: 0.0173 AC: 264 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0369 AC: 128 AN: 3470

East Asian (EAS) AF: 0.00273 AC: 14 AN: 5136

South Asian (SAS) AF: 0.00665 AC: 32 AN: 4812

European-Finnish (FIN) AF: 0.0103 AC: 109 AN: 10554

Middle Eastern (MID) AF: 0.0342 AC: 10 AN: 292

European-Non Finnish (NFE) AF: 0.00431 AC: 293 AN: 68016

Other (OTH) AF: 0.0312 AC: 66 AN: 2114

Alfa AF: 0.0162 Hom.: 116

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
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7079348; hg19: chr10-78072389;