chr5-33967040-C-G

Variant names:

• chr5-33967040-C-G
• rs35412
• NM_016180.5:c.563-3024G>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.563-3024G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 152,176 control chromosomes in the GnomAD database, including 51,762 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 0.80 (51762 hom., cov: 31)
• Consequence: SLC45A2 NM_016180.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 14 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.967 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.563-3024G>C		intron	N/A	NP_057264.4
	SLC45A2	NM_001012509.4		c.563-3024G>C		intron	N/A	NP_001012527.2	Q9UMX9-4
	SLC45A2	NM_001297417.4		c.563-12536G>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.563-3024G>C		intron	N/A	ENSP00000296589.4	Q9UMX9-1
	SLC45A2	ENST00000382102.7	TSL:1	c.563-3024G>C		intron	N/A	ENSP00000371534.3	Q9UMX9-4
	SLC45A2	ENST00000509381.1	TSL:1	c.563-12536G>C		intron	N/A	ENSP00000421100.1	D6RGY6

Frequencies

GnomAD3 genomes AF: 0.798 AC: 121288 AN: 152058 Hom.: 51757 Cov.: 31

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.990

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.947

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.986

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.973

Gnomad OTH AF: 0.769

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

GnomAD4 genome AF: 0.797 AC: 121333 AN: 152176 Hom.: 51762 Cov.: 31 AF XY: 0.785 AC XY: 58433 AN XY: 74408

African (AFR) AF: 0.596 AC: 24725 AN: 41470

American (AMR) AF: 0.648 AC: 9909 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.947 AC: 3286 AN: 3470

East Asian (EAS) AF: 0.397 AC: 2045 AN: 5156

South Asian (SAS) AF: 0.407 AC: 1962 AN: 4820

European-Finnish (FIN) AF: 0.986 AC: 10477 AN: 10622

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.973 AC: 66202 AN: 68028

Other (OTH) AF: 0.765 AC: 1618 AN: 2116

Alfa AF: 0.882 Hom.: 7634

Bravo AF: 0.765

Asia WGS AF: 0.433 AC: 1510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.037
DANN	Benign	0.54
PhyloP100		-1.1
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: rs35412; hg19: chr5-33967145;