rs12245799

Variant names:

• chr10-76207557-T-C
• rs12245799
• NM_001305581.2:c.517-116844T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-76207557-T-C
• chr10-76207557-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.517-116844T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,126 control chromosomes in the GnomAD database, including 6,338 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 0.27 (6338 hom., cov: 32)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.517-116844T>C		intron_variant	Intron 5 of 6	ENST00000611255.5	NP_001292510.1
LRMDA	NM_032024.5	c.433-116844T>C		intron_variant	Intron 4 of 5		NP_114413.1
LRMDA	NR_131178.2	n.871-116844T>C		intron_variant	Intron 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.517-116844T>C		intron_variant	Intron 5 of 6	5	NM_001305581.2	ENSP00000480240.1
LRMDA	ENST00000372499.5	c.433-116844T>C		intron_variant	Intron 4 of 5	1		ENSP00000361577.1
LRMDA	ENST00000593699.5	n.871-116844T>C		intron_variant	Intron 6 of 7	1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40823 AN: 152008 Hom.: 6311 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.269 AC: 40916 AN: 152126 Hom.: 6338 Cov.: 32 AF XY: 0.275 AC XY: 20432 AN XY: 74372

African (AFR) AF: 0.379 AC: 15728 AN: 41468

American (AMR) AF: 0.292 AC: 4455 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 604 AN: 3466

East Asian (EAS) AF: 0.600 AC: 3102 AN: 5170

South Asian (SAS) AF: 0.329 AC: 1587 AN: 4824

European-Finnish (FIN) AF: 0.190 AC: 2010 AN: 10596

Middle Eastern (MID) AF: 0.168 AC: 49 AN: 292

European-Non Finnish (NFE) AF: 0.185 AC: 12566 AN: 68010

Other (OTH) AF: 0.279 AC: 589 AN: 2114

Alfa AF: 0.209 Hom.: 3244

Bravo AF: 0.280

Asia WGS AF: 0.471 AC: 1634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.044
DANN	Benign	0.35
PhyloP100		-2.7
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: rs12245799; hg19: chr10-77967315;