rs40132

chr5-33950598-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016180.5(SLC45A2):c.1156+956T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0735 in 152,150 control chromosomes in the GnomAD database, including 1,253 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 0.074 (1253 hom., cov: 33)
• Consequence: SLC45A2 NM_016180.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.313

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC45A2	NM_016180.5	c.1156+956T>C		intron_variant		ENST00000296589.9
SLC45A2	NM_001012509.4	c.1156+956T>C		intron_variant
SLC45A2	XM_047417259.1	c.916+956T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC45A2	ENST00000296589.9	c.1156+956T>C		intron_variant		1	NM_016180.5	P1
SLC45A2	ENST00000382102.7	c.1156+956T>C		intron_variant		1
SLC45A2	ENST00000510600.1	c.631+956T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0734 AC: 11152 AN: 152032 Hom.: 1240 Cov.: 33

Gnomad AFR AF: 0.0651

Gnomad AMI AF: 0.00989

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.0306

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.0124

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0166

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.0735 AC: 11187 AN: 152150 Hom.: 1253 Cov.: 33 AF XY: 0.0811 AC XY: 6032 AN XY: 74388

Gnomad4 AFR AF: 0.0654

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.0306

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.0124

Gnomad4 NFE AF: 0.0166

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0431 Hom.: 231

Bravo AF: 0.0946

Asia WGS AF: 0.239 AC: 830 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.6
Dann	Benign	0.52

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: rs40132; hg19: chr5-33950703;