rs40132

Variant names:

• chr5-33950598-A-G
• rs40132
• NM_016180.5:c.1156+956T>C

Variant summary

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

The NM_016180.5(SLC45A2):​c.1156+956T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0735 in 152,150 control chromosomes in the GnomAD database, including 1,253 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 0.074 (1253 hom., cov: 33)
• Consequence: SLC45A2 NM_016180.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.313
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC45A2	NM_016180.5	c.1156+956T>C		intron_variant	Intron 5 of 6	ENST00000296589.9	NP_057264.4
SLC45A2	NM_001012509.4	c.1156+956T>C		intron_variant	Intron 5 of 5		NP_001012527.2
SLC45A2	XM_047417259.1	c.916+956T>C		intron_variant	Intron 5 of 6		XP_047273215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC45A2	ENST00000296589.9	c.1156+956T>C		intron_variant	Intron 5 of 6	1	NM_016180.5	ENSP00000296589.4
SLC45A2	ENST00000382102.7	c.1156+956T>C		intron_variant	Intron 5 of 5	1		ENSP00000371534.3
SLC45A2	ENST00000510600.1	c.631+956T>C		intron_variant	Intron 4 of 4	3		ENSP00000424010.1

Frequencies

GnomAD3 genomes AF: 0.0734 AC: 11152 AN: 152032 Hom.: 1240 Cov.: 33

Gnomad AFR AF: 0.0651

Gnomad AMI AF: 0.00989

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.0306

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.0124

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0166

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.0735 AC: 11187 AN: 152150 Hom.: 1253 Cov.: 33 AF XY: 0.0811 AC XY: 6032 AN XY: 74388

African (AFR) AF: 0.0654 AC: 2714 AN: 41520

American (AMR) AF: 0.244 AC: 3729 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0306 AC: 106 AN: 3468

East Asian (EAS) AF: 0.420 AC: 2159 AN: 5142

South Asian (SAS) AF: 0.198 AC: 954 AN: 4814

European-Finnish (FIN) AF: 0.0124 AC: 132 AN: 10606

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0166 AC: 1132 AN: 68024

Other (OTH) AF: 0.103 AC: 217 AN: 2112

Alfa AF: 0.0406 Hom.: 245

Bravo AF: 0.0946

Asia WGS AF: 0.239 AC: 830 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.52
PhyloP100		-0.31
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: rs40132; hg19: chr5-33950703;