rs7099295

Positions:

• chr10-76269115-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001305581.2(LRMDA):​c.517-55286C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 151,828 control chromosomes in the GnomAD database, including 24,908 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 0.56 (24908 hom., cov: 31)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.934

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.517-55286C>G		intron_variant		ENST00000611255.5	NP_001292510.1
LRMDA	NM_032024.5	c.433-55286C>G		intron_variant			NP_114413.1
LRMDA	NR_131178.2	n.871-55286C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.517-55286C>G		intron_variant		5	NM_001305581.2	ENSP00000480240	P1
LRMDA	ENST00000372499.5	c.433-55286C>G		intron_variant		1		ENSP00000361577
LRMDA	ENST00000593699.5	n.871-55286C>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84499 AN: 151710 Hom.: 24856 Cov.: 31

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.557 AC: 84604 AN: 151828 Hom.: 24908 Cov.: 31 AF XY: 0.557 AC XY: 41297 AN XY: 74190

Gnomad4 AFR AF: 0.761

Gnomad4 AMR AF: 0.503

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.568

Gnomad4 SAS AF: 0.607

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.553

Alfa AF: 0.513 Hom.: 2567

Bravo AF: 0.571

Asia WGS AF: 0.588 AC: 2045 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Benign	0.60

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: rs7099295; hg19: chr10-78028873;