NM_001305581.2:c.517-34798C>T

Variant names:

• chr10-76289603-C-T
• rs11001720
• NM_001305581.2:c.517-34798C>T

Variant summary

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

The NM_001305581.2(LRMDA):​c.517-34798C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 151,934 control chromosomes in the GnomAD database, including 24,449 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 0.55 (24449 hom., cov: 31)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.514
• Publications: 3 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.517-34798C>T		intron_variant	Intron 5 of 6	ENST00000611255.5	NP_001292510.1
LOC124902462	XR_007062203.1	n.441G>A		non_coding_transcript_exon_variant	Exon 3 of 3
LRMDA	NM_032024.5	c.433-34798C>T		intron_variant	Intron 4 of 5		NP_114413.1
LRMDA	NR_131178.2	n.871-34798C>T		intron_variant	Intron 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.517-34798C>T		intron_variant	Intron 5 of 6	5	NM_001305581.2	ENSP00000480240.1
LRMDA	ENST00000372499.5	c.433-34798C>T		intron_variant	Intron 4 of 5	1		ENSP00000361577.1
LRMDA	ENST00000593699.5	n.871-34798C>T		intron_variant	Intron 6 of 7	1
ENSG00000304285	ENST00000801795.1	n.186+181G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84051 AN: 151818 Hom.: 24404 Cov.: 31

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.594

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.554 AC: 84150 AN: 151934 Hom.: 24449 Cov.: 31 AF XY: 0.553 AC XY: 41042 AN XY: 74236

African (AFR) AF: 0.744 AC: 30841 AN: 41478

American (AMR) AF: 0.500 AC: 7636 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1886 AN: 3472

East Asian (EAS) AF: 0.594 AC: 3055 AN: 5142

South Asian (SAS) AF: 0.560 AC: 2700 AN: 4818

European-Finnish (FIN) AF: 0.441 AC: 4643 AN: 10538

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.464 AC: 31515 AN: 67914

Other (OTH) AF: 0.555 AC: 1170 AN: 2108

Alfa AF: 0.521 Hom.: 3736

Bravo AF: 0.568

Asia WGS AF: 0.585 AC: 2036 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.57
DANN	Benign	0.72
PhyloP100		-0.51
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: rs11001720; hg19: chr10-78049361;