10-75665367-T-G

Position:

• chr10-75665367-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.131+226873T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,118 control chromosomes in the GnomAD database, including 7,766 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 0.20 (7766 hom., cov: 32)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.32

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRMDA	NM_001305581.2	c.131+226873T>G		intron_variant		ENST00000611255.5
LRMDA	NR_131178.2	n.85+17774T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRMDA	ENST00000611255.5	c.131+226873T>G		intron_variant		5	NM_001305581.2	P1
LRMDA	ENST00000593699.5	n.85+17774T>G		intron_variant, non_coding_transcript_variant		1
LRMDA	ENST00000593817.1	n.92+64036T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30752 AN: 152000 Hom.: 7739 Cov.: 32

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0902

Gnomad ASJ AF: 0.0449

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0335

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0262

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.203 AC: 30831 AN: 152118 Hom.: 7766 Cov.: 32 AF XY: 0.199 AC XY: 14822 AN XY: 74382

Gnomad4 AFR AF: 0.589

Gnomad4 AMR AF: 0.0900

Gnomad4 ASJ AF: 0.0449

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.0335

Gnomad4 NFE AF: 0.0263

Gnomad4 OTH AF: 0.160

Alfa AF: 0.0153 Hom.: 17

Bravo AF: 0.225

Asia WGS AF: 0.258 AC: 896 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	0.079
DANN	Benign	0.43

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2395293; hg19: chr10-77425125;