rs35414

Positions:

• chr5-33969523-T-C

Variant summary

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

The NM_016180.5(SLC45A2):​c.563-5507A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 152,084 control chromosomes in the GnomAD database, including 20,401 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 0.45 (20401 hom., cov: 31)
• Consequence: SLC45A2 NM_016180.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46

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 = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC45A2	NM_016180.5	c.563-5507A>G		intron_variant		ENST00000296589.9	NP_057264.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC45A2	ENST00000296589.9	c.563-5507A>G		intron_variant		1	NM_016180.5	ENSP00000296589	P1

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68435 AN: 151966 Hom.: 20405 Cov.: 31

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.429

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

GnomAD4 genome AF: 0.450 AC: 68417 AN: 152084 Hom.: 20401 Cov.: 31 AF XY: 0.445 AC XY: 33117 AN XY: 74340

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.404

Gnomad4 ASJ AF: 0.637

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.754

Gnomad4 NFE AF: 0.653

Gnomad4 OTH AF: 0.425

Alfa AF: 0.576 Hom.: 23902

Bravo AF: 0.415

Asia WGS AF: 0.140 AC: 491 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	12
DANN	Benign	0.74

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: rs35414; hg19: chr5-33969628;