NM_001305581.2:c.399-389G>A

Variant names:

• chr10-76058277-G-A
• rs1898082
• NM_001305581.2:c.399-389G>A

Variant summary

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

The NM_001305581.2(LRMDA):​c.399-389G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 152,100 control chromosomes in the GnomAD database, including 11,223 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 0.36 (11223 hom., cov: 32)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.561
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.447 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.399-389G>A		intron	N/A	NP_001292510.1
	LRMDA	NM_032024.5		c.315-389G>A		intron	N/A	NP_114413.1
	LRMDA	NR_131178.2		n.753-389G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRMDA	ENST00000611255.5	TSL:5 MANE Select	c.399-389G>A		intron	N/A	ENSP00000480240.1
	LRMDA	ENST00000372499.5	TSL:1	c.315-389G>A		intron	N/A	ENSP00000361577.1
	LRMDA	ENST00000593699.5	TSL:1	n.753-389G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55183 AN: 151982 Hom.: 11220 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.00634

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.363 AC: 55206 AN: 152100 Hom.: 11223 Cov.: 32 AF XY: 0.363 AC XY: 26962 AN XY: 74366

African (AFR) AF: 0.242 AC: 10041 AN: 41502

American (AMR) AF: 0.299 AC: 4574 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1847 AN: 3468

East Asian (EAS) AF: 0.00636 AC: 33 AN: 5190

South Asian (SAS) AF: 0.283 AC: 1364 AN: 4824

European-Finnish (FIN) AF: 0.522 AC: 5522 AN: 10572

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.451 AC: 30649 AN: 67954

Other (OTH) AF: 0.376 AC: 792 AN: 2104

Alfa AF: 0.297 Hom.: 1169

Bravo AF: 0.341

Asia WGS AF: 0.159 AC: 556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.9
DANN	Benign	0.58
PhyloP100		0.56
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: rs1898082; hg19: chr10-77818035;