rs28117

Variant names:

• chr5-33962665-G-A
• rs28117
• NM_016180.5:c.888+1026C>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.888+1026C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 152,212 control chromosomes in the GnomAD database, including 50,747 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 0.79 (50747 hom., cov: 33)
• Consequence: SLC45A2 NM_016180.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.528
• Publications: 8 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC45A2	NM_016180.5	c.888+1026C>T		intron_variant	Intron 3 of 6	ENST00000296589.9	NP_057264.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC45A2	ENST00000296589.9	c.888+1026C>T		intron_variant	Intron 3 of 6	1	NM_016180.5	ENSP00000296589.4
SLC45A2	ENST00000382102.7	c.888+1026C>T		intron_variant	Intron 3 of 5	1		ENSP00000371534.3
SLC45A2	ENST00000509381.1	c.563-8161C>T		intron_variant	Intron 2 of 3	1		ENSP00000421100.1
SLC45A2	ENST00000510600.1	c.363+1026C>T		intron_variant	Intron 2 of 4	3		ENSP00000424010.1

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119643 AN: 152094 Hom.: 50745 Cov.: 33

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.990

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.943

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.986

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.972

Gnomad OTH AF: 0.761

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

GnomAD4 genome AF: 0.786 AC: 119678 AN: 152212 Hom.: 50747 Cov.: 33 AF XY: 0.774 AC XY: 57635 AN XY: 74434

African (AFR) AF: 0.561 AC: 23269 AN: 41468

American (AMR) AF: 0.643 AC: 9839 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.943 AC: 3273 AN: 3470

East Asian (EAS) AF: 0.393 AC: 2037 AN: 5184

South Asian (SAS) AF: 0.403 AC: 1946 AN: 4828

European-Finnish (FIN) AF: 0.986 AC: 10478 AN: 10626

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.972 AC: 66130 AN: 68026

Other (OTH) AF: 0.757 AC: 1598 AN: 2112

Alfa AF: 0.900 Hom.: 216291

Bravo AF: 0.752

Asia WGS AF: 0.426 AC: 1487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.24
DANN	Benign	0.45
PhyloP100		-0.53
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: rs28117; hg19: chr5-33962770;