10-76285505-T-G

Position:

• chr10-76285505-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001305581.2(LRMDA):​c.517-38896T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.03 in 152,266 control chromosomes in the GnomAD database, including 196 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 0.030 (196 hom., cov: 32)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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]

LOC124902462 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRMDA	NM_001305581.2	c.517-38896T>G		intron_variant		ENST00000611255.5
LOC124902462	XR_007062203.1	n.4539A>C		non_coding_transcript_exon_variant	3/3
LRMDA	NM_032024.5	c.433-38896T>G		intron_variant
LRMDA	NR_131178.2	n.871-38896T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRMDA	ENST00000611255.5	c.517-38896T>G		intron_variant		5	NM_001305581.2	P1
LRMDA	ENST00000372499.5	c.433-38896T>G		intron_variant		1
LRMDA	ENST00000593699.5	n.871-38896T>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0299 AC: 4556 AN: 152148 Hom.: 194 Cov.: 32

Gnomad AFR AF: 0.0937

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0129

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.0486

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00146

Gnomad OTH AF: 0.0263

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

GnomAD4 genome AF: 0.0300 AC: 4570 AN: 152266 Hom.: 196 Cov.: 32 AF XY: 0.0290 AC XY: 2156 AN XY: 74458

Gnomad4 AFR AF: 0.0936

Gnomad4 AMR AF: 0.0129

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.0486

Gnomad4 SAS AF: 0.00435

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00146

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.0313 Hom.: 19

Bravo AF: 0.0337

Asia WGS AF: 0.0310 AC: 107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.42
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs7101263; hg19: chr10-78045263;