10-75623811-T-G

Variant names:

• chr10-75623811-T-G
• rs1430331
• NM_001305581.2:c.131+185317T>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.131+185317T>G variant causes a intron change. The variant allele was found at a frequency of 0.708 in 152,146 control chromosomes in the GnomAD database, including 38,348 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 0.71 (38348 hom., cov: 33)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.22
• 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000286715 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.131+185317T>G		intron_variant	Intron 2 of 6	ENST00000611255.5	NP_001292510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.131+185317T>G		intron_variant	Intron 2 of 6	5	NM_001305581.2	ENSP00000480240.1
LRMDA	ENST00000593817.1	n.92+22480T>G		intron_variant	Intron 1 of 1	3
ENSG00000286715	ENST00000670381.1	n.66-3580T>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107579 AN: 152028 Hom.: 38328 Cov.: 33

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.716

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

GnomAD4 genome AF: 0.708 AC: 107656 AN: 152146 Hom.: 38348 Cov.: 33 AF XY: 0.709 AC XY: 52715 AN XY: 74376

African (AFR) AF: 0.625 AC: 25904 AN: 41476

American (AMR) AF: 0.645 AC: 9852 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.707 AC: 2454 AN: 3470

East Asian (EAS) AF: 0.791 AC: 4100 AN: 5186

South Asian (SAS) AF: 0.761 AC: 3670 AN: 4822

European-Finnish (FIN) AF: 0.749 AC: 7940 AN: 10598

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.755 AC: 51319 AN: 67996

Other (OTH) AF: 0.716 AC: 1512 AN: 2112

Alfa AF: 0.739 Hom.: 151297

Bravo AF: 0.694

Asia WGS AF: 0.761 AC: 2648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Benign	0.84
PhyloP100		5.2

Splicing

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

Other links and lift over

dbSNP: rs1430331; hg19: chr10-77383569;