rs1865644

Variant names:

• chr10-76286292-A-G
• rs1865644
• NM_001305581.2:c.517-38109A>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.517-38109A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 151,590 control chromosomes in the GnomAD database, including 20,186 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 0.51 (20186 hom., cov: 33)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129
• Publications: 2 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

LOC124902462 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.517-38109A>G		intron_variant	Intron 5 of 6	ENST00000611255.5	NP_001292510.1
LOC124902462	XR_007062203.1	n.3752T>C		non_coding_transcript_exon_variant	Exon 3 of 3
LRMDA	NM_032024.5	c.433-38109A>G		intron_variant	Intron 4 of 5		NP_114413.1
LRMDA	NR_131178.2	n.871-38109A>G		intron_variant	Intron 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.517-38109A>G		intron_variant	Intron 5 of 6	5	NM_001305581.2	ENSP00000480240.1
LRMDA	ENST00000372499.5	c.433-38109A>G		intron_variant	Intron 4 of 5	1		ENSP00000361577.1
LRMDA	ENST00000593699.5	n.871-38109A>G		intron_variant	Intron 6 of 7	1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77691 AN: 151474 Hom.: 20162 Cov.: 33

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.517

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

GnomAD4 genome AF: 0.513 AC: 77755 AN: 151590 Hom.: 20186 Cov.: 33 AF XY: 0.514 AC XY: 38044 AN XY: 74042

African (AFR) AF: 0.600 AC: 24769 AN: 41282

American (AMR) AF: 0.486 AC: 7405 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1862 AN: 3456

East Asian (EAS) AF: 0.554 AC: 2847 AN: 5142

South Asian (SAS) AF: 0.597 AC: 2864 AN: 4800

European-Finnish (FIN) AF: 0.437 AC: 4586 AN: 10506

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.466 AC: 31601 AN: 67864

Other (OTH) AF: 0.516 AC: 1090 AN: 2114

Alfa AF: 0.493 Hom.: 54510

Bravo AF: 0.523

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.33
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: rs1865644; hg19: chr10-78046050;