rs35390

Positions:

• chr5-33955221-C-A

Variant summary

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

The NM_016180.5(SLC45A2):​c.889-717G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 152,086 control chromosomes in the GnomAD database, including 52,511 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 0.81 (52511 hom., cov: 31)
• Consequence: SLC45A2 NM_016180.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.931

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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC45A2	NM_016180.5	c.889-717G>T		intron_variant		ENST00000296589.9	NP_057264.4
SLC45A2	NM_001012509.4	c.889-717G>T		intron_variant			NP_001012527.2
SLC45A2	NM_001297417.4	c.563-717G>T		intron_variant			NP_001284346.2
SLC45A2	XM_047417259.1	c.649-717G>T		intron_variant			XP_047273215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC45A2	ENST00000296589.9	c.889-717G>T		intron_variant		1	NM_016180.5	ENSP00000296589	P1
SLC45A2	ENST00000382102.7	c.889-717G>T		intron_variant		1		ENSP00000371534
SLC45A2	ENST00000509381.1	c.563-717G>T		intron_variant		1		ENSP00000421100
SLC45A2	ENST00000510600.1	c.364-717G>T		intron_variant		3		ENSP00000424010

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122455 AN: 151968 Hom.: 52503 Cov.: 31

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.990

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.951

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.985

Gnomad MID AF: 0.732

Gnomad NFE AF: 0.975

Gnomad OTH AF: 0.778

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

GnomAD4 genome AF: 0.805 AC: 122505 AN: 152086 Hom.: 52511 Cov.: 31 AF XY: 0.793 AC XY: 58955 AN XY: 74354

Gnomad4 AFR AF: 0.622

Gnomad4 AMR AF: 0.655

Gnomad4 ASJ AF: 0.951

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.985

Gnomad4 NFE AF: 0.975

Gnomad4 OTH AF: 0.774

Alfa AF: 0.923 Hom.: 79127

Bravo AF: 0.774

Asia WGS AF: 0.421 AC: 1471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.72

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: rs35390; hg19: chr5-33955326;