rs4746332

Variant names:

• chr10-75792947-T-C
• rs4746332
• NM_001305581.2:c.132-243061T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-75792947-T-C
• chr10-75792947-T-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.132-243061T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 152,076 control chromosomes in the GnomAD database, including 47,970 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 0.79 (47970 hom., cov: 31)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.530
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.132-243061T>C		intron_variant	Intron 2 of 6	ENST00000611255.5	NP_001292510.1
LRMDA	NM_032024.5	c.47+9925T>C		intron_variant	Intron 1 of 5		NP_114413.1
LRMDA	NR_131178.2	n.86-89709T>C		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.132-243061T>C		intron_variant	Intron 2 of 6	5	NM_001305581.2	ENSP00000480240.1
LRMDA	ENST00000372499.5	c.47+9925T>C		intron_variant	Intron 1 of 5	1		ENSP00000361577.1
LRMDA	ENST00000593699.5	n.86-89709T>C		intron_variant	Intron 1 of 7	1
LRMDA	ENST00000593817.1	n.92+191616T>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.790 AC: 120084 AN: 151958 Hom.: 47912 Cov.: 31

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.959

Gnomad SAS AF: 0.883

Gnomad FIN AF: 0.837

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.722

Gnomad OTH AF: 0.762

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

GnomAD4 genome AF: 0.790 AC: 120202 AN: 152076 Hom.: 47970 Cov.: 31 AF XY: 0.797 AC XY: 59204 AN XY: 74326

African (AFR) AF: 0.873 AC: 36216 AN: 41486

American (AMR) AF: 0.776 AC: 11867 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 2568 AN: 3468

East Asian (EAS) AF: 0.958 AC: 4945 AN: 5160

South Asian (SAS) AF: 0.883 AC: 4255 AN: 4820

European-Finnish (FIN) AF: 0.837 AC: 8839 AN: 10564

Middle Eastern (MID) AF: 0.596 AC: 174 AN: 292

European-Non Finnish (NFE) AF: 0.722 AC: 49103 AN: 67976

Other (OTH) AF: 0.763 AC: 1614 AN: 2114

Alfa AF: 0.759 Hom.: 16838

Bravo AF: 0.790

Asia WGS AF: 0.914 AC: 3179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.58
PhyloP100		-0.53
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: rs4746332; hg19: chr10-77552705;