rs10509360

Variant names:

• chr10-75764376-C-G
• rs10509360
• NM_001305581.2:c.132-271632C>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.132-271632C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0765 in 152,222 control chromosomes in the GnomAD database, including 1,217 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 0.076 (1217 hom., cov: 32)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224
• Publications: 1 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.132-271632C>G		intron_variant	Intron 2 of 6	ENST00000611255.5	NP_001292510.1
LRMDA	NR_131178.2	n.85+116783C>G		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.132-271632C>G		intron_variant	Intron 2 of 6	5	NM_001305581.2	ENSP00000480240.1
LRMDA	ENST00000593699.5	n.85+116783C>G		intron_variant	Intron 1 of 7	1
LRMDA	ENST00000593817.1	n.92+163045C>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.0763 AC: 11613 AN: 152104 Hom.: 1212 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0352

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0390

Gnomad FIN AF: 0.00311

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.00977

Gnomad OTH AF: 0.0684

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

GnomAD4 genome AF: 0.0765 AC: 11643 AN: 152222 Hom.: 1217 Cov.: 32 AF XY: 0.0742 AC XY: 5526 AN XY: 74446

African (AFR) AF: 0.239 AC: 9926 AN: 41496

American (AMR) AF: 0.0352 AC: 538 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 125 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.0386 AC: 186 AN: 4820

European-Finnish (FIN) AF: 0.00311 AC: 33 AN: 10610

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.00981 AC: 667 AN: 68026

Other (OTH) AF: 0.0682 AC: 144 AN: 2112

Alfa AF: 0.0499 Hom.: 97

Bravo AF: 0.0856

Asia WGS AF: 0.0510 AC: 179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.95
DANN	Benign	0.31
PhyloP100		-0.22

Splicing

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

Other links and lift over

dbSNP: rs10509360; hg19: chr10-77524134;