rs35395

Positions:

• chr5-33948484-T-C

Variant summary

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

The ENST00000296589.9(SLC45A2):​c.1157-1110A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 152,112 control chromosomes in the GnomAD database, including 45,031 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 0.70 (45031 hom., cov: 32)
• Consequence: SLC45A2 ENST00000296589.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.936

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC45A2	NM_016180.5	c.1157-1110A>G		intron_variant		ENST00000296589.9	NP_057264.4
SLC45A2	NM_001012509.4	c.1157-1110A>G		intron_variant			NP_001012527.2
SLC45A2	XM_047417259.1	c.917-1110A>G		intron_variant			XP_047273215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC45A2	ENST00000296589.9	c.1157-1110A>G		intron_variant		1	NM_016180.5	ENSP00000296589	P1
SLC45A2	ENST00000382102.7	c.1157-1110A>G		intron_variant		1		ENSP00000371534
SLC45A2	ENST00000510600.1	c.632-1110A>G		intron_variant		3		ENSP00000424010

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106708 AN: 151994 Hom.: 45026 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.990

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.933

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.985

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.969

Gnomad OTH AF: 0.679

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

GnomAD4 genome AF: 0.702 AC: 106726 AN: 152112 Hom.: 45031 Cov.: 32 AF XY: 0.688 AC XY: 51182 AN XY: 74398

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.594

Gnomad4 ASJ AF: 0.933

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.985

Gnomad4 NFE AF: 0.969

Gnomad4 OTH AF: 0.677

Alfa AF: 0.835 Hom.: 17148

Bravo AF: 0.658

Asia WGS AF: 0.248 AC: 867 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.4
DANN	Benign	0.73

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: rs35395; hg19: chr5-33948589;