NM_001305581.2:c.517-52612A>G

Variant names:

• chr10-76271789-A-G
• rs4503472
• NM_001305581.2:c.517-52612A>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.517-52612A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 152,114 control chromosomes in the GnomAD database, including 25,375 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 0.56 (25375 hom., cov: 33)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.758 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.517-52612A>G		intron	N/A	NP_001292510.1
	LRMDA	NM_032024.5		c.433-52612A>G		intron	N/A	NP_114413.1
	LRMDA	NR_131178.2		n.871-52612A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRMDA	ENST00000611255.5	TSL:5 MANE Select	c.517-52612A>G		intron	N/A	ENSP00000480240.1
	LRMDA	ENST00000372499.5	TSL:1	c.433-52612A>G		intron	N/A	ENSP00000361577.1
	LRMDA	ENST00000593699.5	TSL:1	n.871-52612A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85412 AN: 151998 Hom.: 25320 Cov.: 33

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.560

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

GnomAD4 genome AF: 0.562 AC: 85519 AN: 152114 Hom.: 25375 Cov.: 33 AF XY: 0.561 AC XY: 41740 AN XY: 74344

African (AFR) AF: 0.765 AC: 31763 AN: 41518

American (AMR) AF: 0.511 AC: 7812 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1858 AN: 3470

East Asian (EAS) AF: 0.588 AC: 3034 AN: 5160

South Asian (SAS) AF: 0.614 AC: 2963 AN: 4822

European-Finnish (FIN) AF: 0.432 AC: 4562 AN: 10564

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.465 AC: 31604 AN: 67982

Other (OTH) AF: 0.559 AC: 1179 AN: 2110

Alfa AF: 0.547 Hom.: 4604

Bravo AF: 0.577

Asia WGS AF: 0.600 AC: 2089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.8
DANN	Benign	0.47
PhyloP100		-0.14
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: rs4503472; hg19: chr10-78031547;