chr5-33945653-C-T

Variant names:

• chr5-33945653-C-T
• rs35405
• NM_016180.5:c.1369-781G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016180.5(SLC45A2):​c.1369-781G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 151,392 control chromosomes in the GnomAD database, including 9,717 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 0.34 (9717 hom., cov: 32)
• Consequence: SLC45A2 NM_016180.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016180.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC45A2	NM_016180.5	MANE Select	c.1369-781G>A		intron	N/A	NP_057264.4
	SLC45A2	NM_001012509.4		c.*1495G>A		downstream_gene	N/A	NP_001012527.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC45A2	ENST00000296589.9	TSL:1 MANE Select	c.1369-781G>A		intron	N/A	ENSP00000296589.4
	SLC45A2	ENST00000382102.7	TSL:1	c.*1495G>A		downstream_gene	N/A	ENSP00000371534.3

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51328 AN: 151276 Hom.: 9715 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.349

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.339 AC: 51339 AN: 151392 Hom.: 9717 Cov.: 32 AF XY: 0.334 AC XY: 24727 AN XY: 74000

African (AFR) AF: 0.192 AC: 7834 AN: 40902

American (AMR) AF: 0.298 AC: 4554 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1404 AN: 3464

East Asian (EAS) AF: 0.116 AC: 600 AN: 5182

South Asian (SAS) AF: 0.192 AC: 925 AN: 4810

European-Finnish (FIN) AF: 0.441 AC: 4632 AN: 10508

Middle Eastern (MID) AF: 0.348 AC: 101 AN: 290

European-Non Finnish (NFE) AF: 0.443 AC: 30115 AN: 67952

Other (OTH) AF: 0.353 AC: 740 AN: 2098

Alfa AF: 0.399 Hom.: 24623

Bravo AF: 0.319

Asia WGS AF: 0.199 AC: 695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.8
DANN	Benign	0.73
PhyloP100		0.086
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: rs35405; hg19: chr5-33945758;