rs35412

chr5-33967040-C-Gchr5-33967040-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC45A2	NM_016180.5	c.563-3024G>C		intron_variant		ENST00000296589.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC45A2	ENST00000296589.9	c.563-3024G>C		intron_variant		1	NM_016180.5	P1

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

Gnomad4 AFR AF: 0.596

Gnomad4 AMR AF: 0.648

Gnomad4 ASJ AF: 0.947

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.407

Gnomad4 FIN AF: 0.986

Gnomad4 NFE AF: 0.973

Gnomad4 OTH AF: 0.765

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.037
Dann	Benign	0.54

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: rs35412; hg19: chr5-33967145;