10-75665367-T-G

Variant names:

• chr10-75665367-T-G
• rs2395293
• NM_001305581.2:c.131+226873T>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.131+226873T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,118 control chromosomes in the GnomAD database, including 7,766 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 0.20 (7766 hom., cov: 32)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.32
• Publications: 0 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.131+226873T>G		intron_variant	Intron 2 of 6	ENST00000611255.5	NP_001292510.1
LRMDA	NR_131178.2	n.85+17774T>G		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.131+226873T>G		intron_variant	Intron 2 of 6	5	NM_001305581.2	ENSP00000480240.1
LRMDA	ENST00000593699.5	n.85+17774T>G		intron_variant	Intron 1 of 7	1
LRMDA	ENST00000593817.1	n.92+64036T>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30752 AN: 152000 Hom.: 7739 Cov.: 32

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0902

Gnomad ASJ AF: 0.0449

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0335

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0262

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.203 AC: 30831 AN: 152118 Hom.: 7766 Cov.: 32 AF XY: 0.199 AC XY: 14822 AN XY: 74382

African (AFR) AF: 0.589 AC: 24401 AN: 41416

American (AMR) AF: 0.0900 AC: 1376 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0449 AC: 156 AN: 3472

East Asian (EAS) AF: 0.326 AC: 1687 AN: 5170

South Asian (SAS) AF: 0.141 AC: 680 AN: 4822

European-Finnish (FIN) AF: 0.0335 AC: 356 AN: 10618

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0263 AC: 1786 AN: 68014

Other (OTH) AF: 0.160 AC: 337 AN: 2108

Alfa AF: 0.0153 Hom.: 17

Bravo AF: 0.225

Asia WGS AF: 0.258 AC: 896 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.079
DANN	Benign	0.43
PhyloP100		-2.3

Splicing

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

Other links and lift over

dbSNP: rs2395293; hg19: chr10-77425125;