10-76202596-T-C

Variant names:

• chr10-76202596-T-C
• rs11001685
• NM_001305581.2:c.517-121805T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001305581.2(LRMDA):​c.517-121805T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 151,834 control chromosomes in the GnomAD database, including 9,347 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 0.31 (9347 hom., cov: 32)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.128
• Publications: 6 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: Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001305581.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRMDA	NM_001305581.2	MANE Select	c.517-121805T>C		intron	N/A	NP_001292510.1	A0A087WWI0
	LRMDA	NM_032024.5		c.433-121805T>C		intron	N/A	NP_114413.1	Q9H2I8
	LRMDA	NR_131178.2		n.871-121805T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRMDA	ENST00000611255.5	TSL:5 MANE Select	c.517-121805T>C		intron	N/A	ENSP00000480240.1	A0A087WWI0
	LRMDA	ENST00000372499.5	TSL:1	c.433-121805T>C		intron	N/A	ENSP00000361577.1	Q9H2I8
	LRMDA	ENST00000593699.5	TSL:1	n.871-121805T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47549 AN: 151716 Hom.: 9311 Cov.: 32

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.314 AC: 47657 AN: 151834 Hom.: 9347 Cov.: 32 AF XY: 0.318 AC XY: 23584 AN XY: 74200

African (AFR) AF: 0.532 AC: 22006 AN: 41352

American (AMR) AF: 0.314 AC: 4794 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 686 AN: 3468

East Asian (EAS) AF: 0.597 AC: 3071 AN: 5140

South Asian (SAS) AF: 0.327 AC: 1570 AN: 4794

European-Finnish (FIN) AF: 0.190 AC: 2000 AN: 10536

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12591 AN: 67976

Other (OTH) AF: 0.312 AC: 659 AN: 2112

Alfa AF: 0.243 Hom.: 2642

Bravo AF: 0.332

Asia WGS AF: 0.476 AC: 1650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	18
DANN	Benign	0.75
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: rs11001685; hg19: chr10-77962354;