chr10-75779415-T-G

Variant names:

• chr10-75779415-T-G
• rs7080160
• NM_001305581.2:c.132-256593T>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.132-256593T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,998 control chromosomes in the GnomAD database, including 12,861 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 0.38 (12861 hom., cov: 32)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440
• 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=-0.59).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.132-256593T>G		intron_variant	Intron 2 of 6	ENST00000611255.5	NP_001292510.1
LRMDA	NR_131178.2	n.86-103241T>G		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.132-256593T>G		intron_variant	Intron 2 of 6	5	NM_001305581.2	ENSP00000480240.1
LRMDA	ENST00000593699.5	n.86-103241T>G		intron_variant	Intron 1 of 7	1
LRMDA	ENST00000593817.1	n.92+178084T>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57545 AN: 151880 Hom.: 12851 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.379 AC: 57570 AN: 151998 Hom.: 12861 Cov.: 32 AF XY: 0.384 AC XY: 28525 AN XY: 74296

African (AFR) AF: 0.137 AC: 5667 AN: 41458

American (AMR) AF: 0.391 AC: 5972 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1213 AN: 3472

East Asian (EAS) AF: 0.343 AC: 1766 AN: 5148

South Asian (SAS) AF: 0.542 AC: 2607 AN: 4814

European-Finnish (FIN) AF: 0.524 AC: 5535 AN: 10568

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.492 AC: 33408 AN: 67946

Other (OTH) AF: 0.369 AC: 777 AN: 2106

Alfa AF: 0.424 Hom.: 1977

Bravo AF: 0.356

Asia WGS AF: 0.414 AC: 1441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	10
DANN	Benign	0.81
PhyloP100		-0.044

Splicing

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

Other links and lift over

dbSNP: rs7080160; hg19: chr10-77539173;