5-33958854-C-A

Variant names:

• chr5-33958854-C-A
• rs28777
• NM_016180.5:c.889-4350G>T

Variant summary

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

The NM_016180.5(SLC45A2):​c.889-4350G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,160 control chromosomes in the GnomAD database, including 44,405 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 0.69 (44405 hom., cov: 33)
• Consequence: SLC45A2 NM_016180.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.461
• Publications: 75 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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC45A2	NM_016180.5	c.889-4350G>T		intron_variant	Intron 3 of 6	ENST00000296589.9	NP_057264.4
SLC45A2	NM_001012509.4	c.889-4350G>T		intron_variant	Intron 3 of 5		NP_001012527.2
SLC45A2	NM_001297417.4	c.563-4350G>T		intron_variant	Intron 2 of 3		NP_001284346.2
SLC45A2	XM_047417259.1	c.649-4350G>T		intron_variant	Intron 3 of 6		XP_047273215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC45A2	ENST00000296589.9	c.889-4350G>T		intron_variant	Intron 3 of 6	1	NM_016180.5	ENSP00000296589.4
SLC45A2	ENST00000382102.7	c.889-4350G>T		intron_variant	Intron 3 of 5	1		ENSP00000371534.3
SLC45A2	ENST00000509381.1	c.563-4350G>T		intron_variant	Intron 2 of 3	1		ENSP00000421100.1
SLC45A2	ENST00000510600.1	c.364-4350G>T		intron_variant	Intron 2 of 4	3		ENSP00000424010.1

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104645 AN: 152042 Hom.: 44404 Cov.: 33

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.990

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.933

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.985

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.969

Gnomad OTH AF: 0.675

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

GnomAD4 genome AF: 0.688 AC: 104654 AN: 152160 Hom.: 44405 Cov.: 33 AF XY: 0.674 AC XY: 50178 AN XY: 74418

African (AFR) AF: 0.284 AC: 11775 AN: 41472

American (AMR) AF: 0.589 AC: 8997 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.933 AC: 3239 AN: 3470

East Asian (EAS) AF: 0.123 AC: 638 AN: 5178

South Asian (SAS) AF: 0.243 AC: 1173 AN: 4820

European-Finnish (FIN) AF: 0.985 AC: 10460 AN: 10624

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.969 AC: 65866 AN: 68004

Other (OTH) AF: 0.672 AC: 1420 AN: 2112

Alfa AF: 0.856 Hom.: 163287

Bravo AF: 0.642

Asia WGS AF: 0.248 AC: 869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.85
PhyloP100		-0.46
Mutation Taster		=99/1	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: rs28777; hg19: chr5-33958959;