rs955157

Variant names:

• chr10-75814389-A-G
• rs955157
• NM_001305581.2:c.132-221619A>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.132-221619A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 151,964 control chromosomes in the GnomAD database, including 12,949 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 0.38 (12949 hom., cov: 32)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.903
• Publications: 1 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=-0.43).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.5 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.132-221619A>G		intron	N/A	NP_001292510.1	A0A087WWI0
	LRMDA	NM_032024.5		c.47+31367A>G		intron	N/A	NP_114413.1	Q9H2I8
	LRMDA	NR_131178.2		n.86-68267A>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.132-221619A>G		intron	N/A	ENSP00000480240.1	A0A087WWI0
	LRMDA	ENST00000372499.5	TSL:1	c.47+31367A>G		intron	N/A	ENSP00000361577.1	Q9H2I8
	LRMDA	ENST00000593699.5	TSL:1	n.86-68267A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57831 AN: 151846 Hom.: 12942 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.381 AC: 57845 AN: 151964 Hom.: 12949 Cov.: 32 AF XY: 0.384 AC XY: 28554 AN XY: 74270

African (AFR) AF: 0.137 AC: 5680 AN: 41452

American (AMR) AF: 0.401 AC: 6113 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1243 AN: 3468

East Asian (EAS) AF: 0.341 AC: 1760 AN: 5160

South Asian (SAS) AF: 0.517 AC: 2483 AN: 4804

European-Finnish (FIN) AF: 0.521 AC: 5489 AN: 10538

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.495 AC: 33660 AN: 67974

Other (OTH) AF: 0.376 AC: 794 AN: 2110

Alfa AF: 0.418 Hom.: 2759

Bravo AF: 0.358

Asia WGS AF: 0.396 AC: 1378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	16
DANN	Benign	0.82
PhyloP100		0.90
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: rs955157; hg19: chr10-77574147;