rs7099295

Variant names:

• chr10-76269115-C-G
• rs7099295
• NM_001305581.2:c.517-55286C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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: Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001305581.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRMDA	NM_001305581.2	MANE Select	c.517-55286C>G		intron	N/A	NP_001292510.1	A0A087WWI0
	LRMDA	NM_032024.5		c.433-55286C>G		intron	N/A	NP_114413.1	Q9H2I8
	LRMDA	NR_131178.2		n.871-55286C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRMDA	ENST00000611255.5	TSL:5 MANE Select	c.517-55286C>G		intron	N/A	ENSP00000480240.1	A0A087WWI0
	LRMDA	ENST00000372499.5	TSL:1	c.433-55286C>G		intron	N/A	ENSP00000361577.1	Q9H2I8
	LRMDA	ENST00000593699.5	TSL:1	n.871-55286C>G		intron	N/A

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

African (AFR) AF: 0.761 AC: 31504 AN: 41384

American (AMR) AF: 0.503 AC: 7663 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1842 AN: 3470

East Asian (EAS) AF: 0.568 AC: 2927 AN: 5156

South Asian (SAS) AF: 0.607 AC: 2913 AN: 4796

European-Finnish (FIN) AF: 0.437 AC: 4599 AN: 10516

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.460 AC: 31290 AN: 67950

Other (OTH) AF: 0.553 AC: 1165 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Benign	0.60
PhyloP100		0.93
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: rs7099295; hg19: chr10-78028873;