chr10-75538851-A-G

Position:

• chr10-75538851-A-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+100357A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0433 in 152,248 control chromosomes in the GnomAD database, including 237 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 0.043 (237 hom., cov: 32)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

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=-0.57).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.131+100357A>G		intron_variant		ENST00000611255.5	NP_001292510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.131+100357A>G		intron_variant		5	NM_001305581.2	ENSP00000480240.1

Frequencies

GnomAD3 genomes AF: 0.0433 AC: 6582 AN: 152130 Hom.: 238 Cov.: 32

Gnomad AFR AF: 0.00978

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0331

Gnomad EAS AF: 0.0480

Gnomad SAS AF: 0.0709

Gnomad FIN AF: 0.0373

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0445

Gnomad OTH AF: 0.0402

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

GnomAD4 genome AF: 0.0433 AC: 6590 AN: 152248 Hom.: 237 Cov.: 32 AF XY: 0.0463 AC XY: 3446 AN XY: 74450

Gnomad4 AFR AF: 0.00975

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.0331

Gnomad4 EAS AF: 0.0485

Gnomad4 SAS AF: 0.0707

Gnomad4 FIN AF: 0.0373

Gnomad4 NFE AF: 0.0445

Gnomad4 OTH AF: 0.0436

Alfa AF: 0.0431 Hom.: 189

Bravo AF: 0.0492

Asia WGS AF: 0.0830 AC: 287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	1.1
DANN	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2043090; hg19: chr10-77298609;