chr10-76539893-A-G

Variant names:

• chr10-76539893-A-G
• rs1907308
• NM_001305581.2:c.602-17316A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001305581.2(LRMDA):​c.602-17316A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 151,890 control chromosomes in the GnomAD database, including 6,975 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 0.29 (6975 hom., cov: 32)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.72
• Publications: 5 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.355 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRMDA	NM_001305581.2	MANE Select	c.602-17316A>G		intron	N/A	NP_001292510.1
	LRMDA	NM_032024.5		c.518-17316A>G		intron	N/A	NP_114413.1
	LRMDA	NR_131178.2		n.956-17316A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRMDA	ENST00000611255.5	TSL:5 MANE Select	c.602-17316A>G		intron	N/A	ENSP00000480240.1
	LRMDA	ENST00000372499.5	TSL:1	c.518-17316A>G		intron	N/A	ENSP00000361577.1
	LRMDA	ENST00000593699.5	TSL:1	n.956-17316A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44010 AN: 151770 Hom.: 6976 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.0345

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.290 AC: 44038 AN: 151890 Hom.: 6975 Cov.: 32 AF XY: 0.285 AC XY: 21175 AN XY: 74220

African (AFR) AF: 0.238 AC: 9852 AN: 41432

American (AMR) AF: 0.210 AC: 3213 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 847 AN: 3468

East Asian (EAS) AF: 0.0345 AC: 178 AN: 5154

South Asian (SAS) AF: 0.197 AC: 945 AN: 4796

European-Finnish (FIN) AF: 0.344 AC: 3626 AN: 10534

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24398 AN: 67922

Other (OTH) AF: 0.262 AC: 553 AN: 2114

Alfa AF: 0.326 Hom.: 1009

Bravo AF: 0.276

Asia WGS AF: 0.134 AC: 466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Benign	0.70
PhyloP100		2.7
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: rs1907308; hg19: chr10-78299651;