Genetic Variant STEAP4:c.*2542A>G (chr7-88276856-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_024636.4(STEAP4):c.*2542A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 152,276 control chromosomes in the GnomAD database, including 24,042 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 0.56 ( 24008 hom., cov: 32)

Exomes 𝑓: 0.53 ( 34 hom. )

Consequence

STEAP4
NM_024636.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.46

Publications

18 publications found

Variant links:

Genes affected

STEAP4 (HGNC:21923): (STEAP4 metalloreductase) The protein encoded by this gene belongs to the STEAP (six transmembrane epithelial antigen of prostate) family, and resides in the golgi apparatus. It functions as a metalloreductase that has the ability to reduce both Fe(3+) to Fe(2+) and Cu(2+) to Cu(1+), using NAD(+) as acceptor. Studies in mice and human suggest that this gene maybe involved in adipocyte development and metabolism, and may contribute to the normal biology of the prostate cell, as well as prostate cancer progression. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2011]

STEAP4 links:

SRI-AS1 (HGNC:40564): (SRI antisense RNA 1)

SRI-AS1 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=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
STEAP4	NM_024636.4 link	c.*2542A>G	3_prime_UTR_variant	Exon 5 of 5	ENST00000380079.9	NP_078912.2
STEAP4	NM_001205315.2 link	c.*2542A>G	3_prime_UTR_variant	Exon 6 of 6		NP_001192244.1
STEAP4	NM_001205316.2 link	c.*2542A>G	3_prime_UTR_variant	Exon 4 of 4		NP_001192245.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STEAP4	ENST00000380079.9 link	c.*2542A>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_024636.4	ENSP00000369419.4

Frequencies

GnomAD3 genomes

AF:

0.556

AC:

84398

AN:

151888

Hom.:

23996

Cov.:

show subpopulations

Gnomad AFR

AF:

0.449

Gnomad AMI

AF:

0.624

Gnomad AMR

AF:

0.620

Gnomad ASJ

AF:

0.565

Gnomad EAS

AF:

0.836

Gnomad SAS

AF:

0.653

Gnomad FIN

AF:

0.525

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.581

Gnomad OTH

AF:

0.561

GnomAD4 exome

AF:

0.530

AC:

143

AN:

270

Hom.:

Cov.:

AF XY:

0.532

AC XY:

AN XY:

124

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.875

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.484

AC:

AN:

182

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.552

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.556

AC:

84449

AN:

152006

Hom.:

24008

Cov.:

AF XY:

0.555

AC XY:

41256

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.449

AC:

18622

AN:

41464

American (AMR)

AF:

0.619

AC:

9460

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.565

AC:

1958

AN:

3468

East Asian (EAS)

AF:

0.836

AC:

4312

AN:

5160

South Asian (SAS)

AF:

0.653

AC:

3149

AN:

4822

European-Finnish (FIN)

AF:

0.525

AC:

5533

AN:

10536

Middle Eastern (MID)

AF:

0.507

AC:

149

AN:

294

European-Non Finnish (NFE)

AF:

0.581

AC:

39517

AN:

67968

Other (OTH)

AF:

0.559

AC:

1180

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1898

3796

5695

7593

9491

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

738

1476

2214

2952

3690

<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:

0.572

Hom.:

41344

Bravo

AF:

0.558

Asia WGS

AF:

0.710

AC:

2467

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.8

(source)

DANN

Benign

0.77

PhyloP100

-1.5

Mutation Taster

=99/1

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