10-75569514-G-T

Variant names:

• chr10-75569514-G-T
• rs4746308
• NM_001305581.2:c.131+131020G>T

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+131020G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0917 in 152,226 control chromosomes in the GnomAD database, including 869 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 0.092 (869 hom., cov: 33)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• Publications: 2 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.131+131020G>T		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+131020G>T		intron_variant	Intron 2 of 6	5	NM_001305581.2	ENSP00000480240.1

Frequencies

GnomAD3 genomes AF: 0.0917 AC: 13944 AN: 152108 Hom.: 865 Cov.: 33

Gnomad AFR AF: 0.0422

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0928

Gnomad ASJ AF: 0.0775

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0950

Gnomad OTH AF: 0.0842

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

GnomAD4 genome AF: 0.0917 AC: 13953 AN: 152226 Hom.: 869 Cov.: 33 AF XY: 0.0946 AC XY: 7036 AN XY: 74410

African (AFR) AF: 0.0422 AC: 1753 AN: 41550

American (AMR) AF: 0.0928 AC: 1420 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0775 AC: 269 AN: 3470

East Asian (EAS) AF: 0.316 AC: 1633 AN: 5172

South Asian (SAS) AF: 0.213 AC: 1026 AN: 4826

European-Finnish (FIN) AF: 0.107 AC: 1135 AN: 10584

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0950 AC: 6462 AN: 68012

Other (OTH) AF: 0.0890 AC: 188 AN: 2112

Alfa AF: 0.0899 Hom.: 117

Bravo AF: 0.0868

Asia WGS AF: 0.232 AC: 807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	15
DANN	Benign	0.66
PhyloP100		1.1

Splicing

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

Other links and lift over

dbSNP: rs4746308; hg19: chr10-77329272;