10-75538851-A-G

Variant names:

• chr10-75538851-A-G
• rs2043090
• NM_001305581.2:c.131+100357A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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 -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.

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.131+100357A>G		intron	N/A	NP_001292510.1	A0A087WWI0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRMDA	ENST00000611255.5	TSL:5 MANE Select	c.131+100357A>G		intron	N/A	ENSP00000480240.1	A0A087WWI0

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

African (AFR) AF: 0.00975 AC: 405 AN: 41552

American (AMR) AF: 0.126 AC: 1932 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0331 AC: 115 AN: 3472

East Asian (EAS) AF: 0.0485 AC: 251 AN: 5174

South Asian (SAS) AF: 0.0707 AC: 341 AN: 4822

European-Finnish (FIN) AF: 0.0373 AC: 396 AN: 10612

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0445 AC: 3029 AN: 68012

Other (OTH) AF: 0.0436 AC: 92 AN: 2112

Alfa AF: 0.0428 Hom.: 312

Bravo AF: 0.0492

Asia WGS AF: 0.0830 AC: 287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	1.1
DANN	Benign	0.79
PhyloP100		-1.4
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

Other links and lift over

dbSNP: rs2043090; hg19: chr10-77298609;