rs250412

Variant names:

• chr5-33982939-A-G
• rs250412
• NM_016180.5:c.386-527T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016180.5(SLC45A2):​c.386-527T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 152,166 control chromosomes in the GnomAD database, including 20,366 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 0.50 (20366 hom., cov: 33)
• Consequence: SLC45A2 NM_016180.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770
• Publications: 10 publications found

Genes affected

SLC45A2 (HGNC:16472): (solute carrier family 45 member 2) This gene encodes a transporter protein that mediates melanin synthesis. The protein is expressed in a high percentage of melanoma cell lines. Mutations in this gene are a cause of oculocutaneous albinism type 4, and polymorphisms in this gene are associated with variations in skin and hair color. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

SLC45A2 Gene-Disease associations (from GenCC):

• oculocutaneous albinism type 4

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, G2P, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016180.5. 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
	SLC45A2	NM_016180.5	MANE Select	c.386-527T>C		intron	N/A	NP_057264.4
	SLC45A2	NM_001012509.4		c.386-527T>C		intron	N/A	NP_001012527.2	Q9UMX9-4
	SLC45A2	NM_001297417.4		c.386-527T>C		intron	N/A	NP_001284346.2	D6RGY6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC45A2	ENST00000296589.9	TSL:1 MANE Select	c.386-527T>C		intron	N/A	ENSP00000296589.4	Q9UMX9-1
	SLC45A2	ENST00000382102.7	TSL:1	c.386-527T>C		intron	N/A	ENSP00000371534.3	Q9UMX9-4
	SLC45A2	ENST00000509381.1	TSL:1	c.386-527T>C		intron	N/A	ENSP00000421100.1	D6RGY6

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75578 AN: 152048 Hom.: 20372 Cov.: 33

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.497 AC: 75580 AN: 152166 Hom.: 20366 Cov.: 33 AF XY: 0.494 AC XY: 36730 AN XY: 74380

African (AFR) AF: 0.310 AC: 12878 AN: 41514

American (AMR) AF: 0.468 AC: 7153 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2012 AN: 3470

East Asian (EAS) AF: 0.446 AC: 2308 AN: 5172

South Asian (SAS) AF: 0.225 AC: 1087 AN: 4832

European-Finnish (FIN) AF: 0.673 AC: 7122 AN: 10584

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.608 AC: 41360 AN: 67990

Other (OTH) AF: 0.481 AC: 1016 AN: 2112

Alfa AF: 0.568 Hom.: 99351

Bravo AF: 0.480

Asia WGS AF: 0.314 AC: 1095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.33
PhyloP100		-0.077
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs250412; hg19: chr5-33983044;