rs250416

Positions:

• chr5-33947439-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000296589.9(SLC45A2):​c.1157-65G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0559 in 1,409,144 control chromosomes in the GnomAD database, including 9,737 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.072 (1248 hom., cov: 33)
  • Exomes 𝑓: 0.054 (8489 hom.)
• Consequence: SLC45A2 ENST00000296589.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.612

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 5-33947439-C-A is Benign according to our data. Variant chr5-33947439-C-A is described in ClinVar as [Benign]. Clinvar id is 1261617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC45A2	NM_016180.5	c.1157-65G>T		intron_variant		ENST00000296589.9	NP_057264.4
SLC45A2	NM_001012509.4	c.1157-65G>T		intron_variant			NP_001012527.2
SLC45A2	XM_047417259.1	c.917-65G>T		intron_variant			XP_047273215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC45A2	ENST00000296589.9	c.1157-65G>T		intron_variant		1	NM_016180.5	ENSP00000296589	P1
SLC45A2	ENST00000382102.7	c.1157-65G>T		intron_variant		1		ENSP00000371534
SLC45A2	ENST00000510600.1	c.632-65G>T		intron_variant		3		ENSP00000424010

Frequencies

GnomAD3 genomes AF: 0.0720 AC: 10962 AN: 152178 Hom.: 1234 Cov.: 33

Gnomad AFR AF: 0.0607

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.0309

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.0124

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0166

Gnomad OTH AF: 0.102

GnomAD4 exome AF: 0.0539 AC: 67795 AN: 1256848 Hom.: 8489 AF XY: 0.0574 AC XY: 36488 AN XY: 635146

Gnomad4 AFR exome AF: 0.0620

Gnomad4 AMR exome AF: 0.362

Gnomad4 ASJ exome AF: 0.0314

Gnomad4 EAS exome AF: 0.392

Gnomad4 SAS exome AF: 0.198

Gnomad4 FIN exome AF: 0.0136

Gnomad4 NFE exome AF: 0.0138

Gnomad4 OTH exome AF: 0.0715

GnomAD4 genome AF: 0.0722 AC: 10999 AN: 152296 Hom.: 1248 Cov.: 33 AF XY: 0.0798 AC XY: 5946 AN XY: 74468

Gnomad4 AFR AF: 0.0611

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.0309

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.0124

Gnomad4 NFE AF: 0.0166

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0515 Hom.: 519

Bravo AF: 0.0931

Asia WGS AF: 0.239 AC: 831 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs250416; hg19: chr5-33947544;