NM_001305581.2:c.132-28272T>C

Variant names:

• chr10-76007736-T-C
• rs4745805
• NM_001305581.2:c.132-28272T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001305581.2(LRMDA):​c.132-28272T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,092 control chromosomes in the GnomAD database, including 9,710 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 0.33 (9710 hom., cov: 32)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.132-28272T>C		intron_variant	Intron 2 of 6	ENST00000611255.5	NP_001292510.1
LRMDA	NM_032024.5	c.48-28272T>C		intron_variant	Intron 1 of 5		NP_114413.1
LRMDA	NR_131178.2	n.486-28272T>C		intron_variant	Intron 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.132-28272T>C		intron_variant	Intron 2 of 6	5	NM_001305581.2	ENSP00000480240.1
LRMDA	ENST00000372499.5	c.48-28272T>C		intron_variant	Intron 1 of 5	1		ENSP00000361577.1
LRMDA	ENST00000593699.5	n.486-28272T>C		intron_variant	Intron 3 of 7	1
LRMDA	ENST00000593817.1	n.93-28272T>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50348 AN: 151976 Hom.: 9707 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.0114

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.331 AC: 50347 AN: 152092 Hom.: 9710 Cov.: 32 AF XY: 0.329 AC XY: 24444 AN XY: 74346

African (AFR) AF: 0.182 AC: 7569 AN: 41498

American (AMR) AF: 0.287 AC: 4393 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1641 AN: 3468

East Asian (EAS) AF: 0.0112 AC: 58 AN: 5174

South Asian (SAS) AF: 0.258 AC: 1245 AN: 4818

European-Finnish (FIN) AF: 0.453 AC: 4789 AN: 10562

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.435 AC: 29560 AN: 67976

Other (OTH) AF: 0.357 AC: 751 AN: 2104

Alfa AF: 0.378 Hom.: 1778

Bravo AF: 0.312

Asia WGS AF: 0.145 AC: 506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	18
DANN	Benign	0.66
PhyloP100		2.0
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: rs4745805; hg19: chr10-77767494;