Genetic Variant SLC45A2:c.*682T>C (chr5-33946466-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000382102.7(SLC45A2):c.*682T>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 0.908 in 985,534 control chromosomes in the GnomAD database, including 425,705 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 0.72 ( 45957 hom., cov: 33)

Exomes 𝑓: 0.94 ( 379748 hom. )

Consequence

SLC45A2
ENST00000382102.7 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.393

Publications

26 publications found

Variant links:

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

SLC45A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
SLC45A2	NM_016180.5 link	c.1368+697T>C	intron_variant	Intron 6 of 6	ENST00000296589.9	NP_057264.4
SLC45A2	NM_001012509.4 link	c.*682T>C	3_prime_UTR_variant	Exon 6 of 6		NP_001012527.2
SLC45A2	XM_047417259.1 link	c.1128+697T>C	intron_variant	Intron 6 of 6		XP_047273215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC45A2	ENST00000382102.7 link	c.*682T>C		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000371534.3
SLC45A2	ENST00000296589.9 link	c.1368+697T>C		intron_variant	Intron 6 of 6	1	NM_016180.5	ENSP00000296589.4

Frequencies

GnomAD3 genomes

AF:

0.718

AC:

109163

AN:

152120

Hom.:

45943

Cov.:

show subpopulations

Gnomad AFR

AF:

0.385

Gnomad AMI

AF:

0.990

Gnomad AMR

AF:

0.601

Gnomad ASJ

AF:

0.935

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.244

Gnomad FIN

AF:

0.985

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.969

Gnomad OTH

AF:

0.695

GnomAD4 exome

AF:

0.942

AC:

785300

AN:

833296

Hom.:

379748

Cov.:

AF XY:

0.942

AC XY:

362503

AN XY:

384804

show subpopulations

African (AFR)

AF:

0.330

AC:

5213

AN:

15784

American (AMR)

AF:

0.545

AC:

541

AN:

992

Ashkenazi Jewish (ASJ)

AF:

0.935

AC:

4819

AN:

5152

East Asian (EAS)

AF:

0.117

AC:

426

AN:

3630

South Asian (SAS)

AF:

0.252

AC:

4142

AN:

16466

European-Finnish (FIN)

AF:

0.996

AC:

277

AN:

278

Middle Eastern (MID)

AF:

0.563

AC:

912

AN:

1620

European-Non Finnish (NFE)

AF:

0.980

AC:

746466

AN:

762074

Other (OTH)

AF:

0.824

AC:

22504

AN:

27300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

1493

2986

4480

5973

7466

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20000

40000

60000

80000

100000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.717

AC:

109206

AN:

152238

Hom.:

45957

Cov.:

AF XY:

0.704

AC XY:

52403

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.385

AC:

15975

AN:

41500

American (AMR)

AF:

0.600

AC:

9180

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.935

AC:

3248

AN:

3472

East Asian (EAS)

AF:

0.125

AC:

647

AN:

5182

South Asian (SAS)

AF:

0.247

AC:

1193

AN:

4824

European-Finnish (FIN)

AF:

0.985

AC:

10461

AN:

10622

Middle Eastern (MID)

AF:

0.646

AC:

190

AN:

294

European-Non Finnish (NFE)

AF:

0.969

AC:

65943

AN:

68022

Other (OTH)

AF:

0.694

AC:

1468

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

886

1772

2659

3545

4431

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

736

1472

2208

2944

3680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.841

Hom.:

124753

Bravo

AF:

0.676

Asia WGS

AF:

0.263

AC:

919

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.6

(source)

DANN

Benign

0.53

PhyloP100

-0.39

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over