chr5-33951446-A-G

Variant names:

• chr5-33951446-A-G
• rs2278007
• ENST00000509381.1:c.*206T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001297417.4(SLC45A2):​c.*206T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0293 in 1,602,262 control chromosomes in the GnomAD database, including 3,570 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.058 (596 hom., cov: 32)
  • Exomes 𝑓: 0.026 (2974 hom.)
• Consequence: SLC45A2 NM_001297417.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.21
• Publications: 3 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, G2P, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 5-33951446-A-G is Benign according to our data. Variant chr5-33951446-A-G is described in ClinVar as Benign. ClinVar VariationId is 1222285.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001297417.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC45A2	NM_016180.5	MANE Select	c.1156+108T>C		intron	N/A	NP_057264.4
	SLC45A2	NM_001297417.4		c.*206T>C		3_prime_UTR	Exon 4 of 4	NP_001284346.2	D6RGY6
	SLC45A2	NM_001012509.4		c.1156+108T>C		intron	N/A	NP_001012527.2	Q9UMX9-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC45A2	ENST00000509381.1	TSL:1	c.*206T>C		3_prime_UTR	Exon 4 of 4	ENSP00000421100.1	D6RGY6
	SLC45A2	ENST00000296589.9	TSL:1 MANE Select	c.1156+108T>C		intron	N/A	ENSP00000296589.4	Q9UMX9-1
	SLC45A2	ENST00000382102.7	TSL:1	c.1156+108T>C		intron	N/A	ENSP00000371534.3	Q9UMX9-4

Frequencies

GnomAD3 genomes AF: 0.0577 AC: 8782 AN: 152140 Hom.: 594 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0474

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.00539

Gnomad OTH AF: 0.0642

GnomAD2 exomes AF: 0.0588 AC: 14017 AN: 238380 AF XY: 0.0604

Gnomad AFR exome AF: 0.137

Gnomad AMR exome AF: 0.0448

Gnomad ASJ exome AF: 0.0181

Gnomad EAS exome AF: 0.267

Gnomad FIN exome AF: 0.000556

Gnomad NFE exome AF: 0.00734

Gnomad OTH exome AF: 0.0419

GnomAD4 exome AF: 0.0263 AC: 38164 AN: 1450000 Hom.: 2974 Cov.: 30 AF XY: 0.0299 AC XY: 21547 AN XY: 721524

African (AFR) AF: 0.136 AC: 4505 AN: 33136

American (AMR) AF: 0.0456 AC: 2009 AN: 44088

Ashkenazi Jewish (ASJ) AF: 0.0169 AC: 437 AN: 25914

East Asian (EAS) AF: 0.255 AC: 10115 AN: 39636

South Asian (SAS) AF: 0.148 AC: 12669 AN: 85422

European-Finnish (FIN) AF: 0.000781 AC: 37 AN: 47378

Middle Eastern (MID) AF: 0.0947 AC: 425 AN: 4490

European-Non Finnish (NFE) AF: 0.00477 AC: 5293 AN: 1110000

Other (OTH) AF: 0.0446 AC: 2674 AN: 59936

GnomAD4 genome AF: 0.0578 AC: 8797 AN: 152262 Hom.: 596 Cov.: 32 AF XY: 0.0600 AC XY: 4464 AN XY: 74454

African (AFR) AF: 0.129 AC: 5338 AN: 41508

American (AMR) AF: 0.0475 AC: 727 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3472

East Asian (EAS) AF: 0.268 AC: 1386 AN: 5174

South Asian (SAS) AF: 0.155 AC: 748 AN: 4824

European-Finnish (FIN) AF: 0.000753 AC: 8 AN: 10624

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.00538 AC: 366 AN: 68036

Other (OTH) AF: 0.0634 AC: 134 AN: 2112

Alfa AF: 0.0333 Hom.: 379

Bravo AF: 0.0632

Asia WGS AF: 0.164 AC: 570 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	10
DANN	Benign	0.80
PhyloP100		2.2
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: rs2278007; hg19: chr5-33951551; COSMIC: COSV56869772;