rs28117

Positions:

• chr5-33962665-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
SLC45A2	NM_016180.5	c.888+1026C>T		intron_variant		ENST00000296589.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC45A2	ENST00000296589.9	c.888+1026C>T		intron_variant		1	NM_016180.5	P1
SLC45A2	ENST00000382102.7	c.888+1026C>T		intron_variant		1
SLC45A2	ENST00000509381.1	c.563-8161C>T		intron_variant		1
SLC45A2	ENST00000510600.1	c.363+1026C>T		intron_variant		3

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

Gnomad4 AFR AF: 0.561

Gnomad4 AMR AF: 0.643

Gnomad4 ASJ AF: 0.943

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.403

Gnomad4 FIN AF: 0.986

Gnomad4 NFE AF: 0.972

Gnomad4 OTH AF: 0.757

Alfa AF: 0.929 Hom.: 96383

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs28117; hg19: chr5-33962770;