rs35389

Variant names:

• chr5-33954775-G-A
• rs35389
• NM_016180.5:c.889-271C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

SLC45A2 Gene-Disease associations (from GenCC):

• oculocutaneous albinism type 4

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
SLC45A2	NM_016180.5	c.889-271C>T		intron_variant	Intron 3 of 6	ENST00000296589.9	NP_057264.4
SLC45A2	NM_001012509.4	c.889-271C>T		intron_variant	Intron 3 of 5		NP_001012527.2
SLC45A2	NM_001297417.4	c.563-271C>T		intron_variant	Intron 2 of 3		NP_001284346.2
SLC45A2	XM_047417259.1	c.649-271C>T		intron_variant	Intron 3 of 6		XP_047273215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC45A2	ENST00000296589.9	c.889-271C>T		intron_variant	Intron 3 of 6	1	NM_016180.5	ENSP00000296589.4
SLC45A2	ENST00000382102.7	c.889-271C>T		intron_variant	Intron 3 of 5	1		ENSP00000371534.3
SLC45A2	ENST00000509381.1	c.563-271C>T		intron_variant	Intron 2 of 3	1		ENSP00000421100.1
SLC45A2	ENST00000510600.1	c.364-271C>T		intron_variant	Intron 2 of 4	3		ENSP00000424010.1

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

African (AFR) AF: 0.284 AC: 11765 AN: 41448

American (AMR) AF: 0.588 AC: 8980 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.934 AC: 3240 AN: 3470

East Asian (EAS) AF: 0.123 AC: 634 AN: 5156

South Asian (SAS) AF: 0.244 AC: 1176 AN: 4826

European-Finnish (FIN) AF: 0.985 AC: 10461 AN: 10624

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.969 AC: 65877 AN: 68010

Other (OTH) AF: 0.673 AC: 1422 AN: 2112

Alfa AF: 0.783 Hom.: 15086

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

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.039
DANN	Benign	0.48
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35389; hg19: chr5-33954880;