rs35389

Positions:

• chr5-33954775-G-A
• chr5-33954775-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016180.5(SLC45A2):​c.889-271C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,116 control chromosomes in the GnomAD database, including 44,408 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.69 (44408 hom., cov: 31)
• Consequence: SLC45A2 NM_016180.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.692

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 5-33954775-G-A is Benign according to our data. Variant chr5-33954775-G-A is described in ClinVar as [Benign]. Clinvar id is 1229130.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC45A2	NM_016180.5	c.889-271C>T		intron_variant		ENST00000296589.9	NP_057264.4
SLC45A2	NM_001012509.4	c.889-271C>T		intron_variant			NP_001012527.2
SLC45A2	NM_001297417.4	c.563-271C>T		intron_variant			NP_001284346.2
SLC45A2	XM_047417259.1	c.649-271C>T		intron_variant			XP_047273215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC45A2	ENST00000296589.9	c.889-271C>T		intron_variant		1	NM_016180.5	ENSP00000296589	P1
SLC45A2	ENST00000382102.7	c.889-271C>T		intron_variant		1		ENSP00000371534
SLC45A2	ENST00000509381.1	c.563-271C>T		intron_variant		1		ENSP00000421100
SLC45A2	ENST00000510600.1	c.364-271C>T		intron_variant		3		ENSP00000424010

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104632 AN: 151998 Hom.: 44407 Cov.: 31

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.990

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.934

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.985

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.969

Gnomad OTH AF: 0.676

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

GnomAD4 genome AF: 0.688 AC: 104640 AN: 152116 Hom.: 44408 Cov.: 31 AF XY: 0.675 AC XY: 50172 AN XY: 74364

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.588

Gnomad4 ASJ AF: 0.934

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.985

Gnomad4 NFE AF: 0.969

Gnomad4 OTH AF: 0.673

Alfa AF: 0.783 Hom.: 14136

Bravo AF: 0.642

Asia WGS AF: 0.248 AC: 867 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.039
DANN	Benign	0.48

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: rs35389; hg19: chr5-33954880;