Variant chr7-88284046-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024636.4(STEAP4):c.224G>A(p.Gly75Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 1,614,030 control chromosomes in the GnomAD database, including 468,113 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.81 ( 50618 hom., cov: 31)

Exomes 𝑓: 0.75 ( 417495 hom. )

Consequence

STEAP4
NM_024636.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.753

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:

ENSG00000228113 (HGNC:):

ENSG00000228113 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.349E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
STEAP4	NM_024636.4 link	c.224G>A	p.Gly75Asp	missense_variant	Exon 2 of 5	ENST00000380079.9	NP_078912.2
STEAP4	NM_001205315.2 link	c.224G>A	p.Gly75Asp	missense_variant	Exon 3 of 6		NP_001192244.1
STEAP4	NM_001205316.2 link	c.224G>A	p.Gly75Asp	missense_variant	Exon 2 of 4		NP_001192245.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STEAP4	ENST00000380079.9 link	c.224G>A	p.Gly75Asp	missense_variant	Exon 2 of 5	1	NM_024636.4	ENSP00000369419.4		Q687X5-1

Frequencies

GnomAD3 genomes

AF:

0.810

AC:

123196

AN:

152066

Hom.:

50562

Cov.:

show subpopulations

Gnomad AFR

AF:

0.951

Gnomad AMI

AF:

0.796

Gnomad AMR

AF:

0.782

Gnomad ASJ

AF:

0.745

Gnomad EAS

AF:

0.905

Gnomad SAS

AF:

0.780

Gnomad FIN

AF:

0.724

Gnomad MID

AF:

0.718

Gnomad NFE

AF:

0.743

Gnomad OTH

AF:

0.792

GnomAD3 exomes

AF:

0.776

AC:

193402

AN:

249344

Hom.:

75459

AF XY:

0.772

AC XY:

104441

AN XY:

135288

show subpopulations

Gnomad AFR exome

AF:

0.958

Gnomad AMR exome

AF:

0.795

Gnomad ASJ exome

AF:

0.755

Gnomad EAS exome

AF:

0.899

Gnomad SAS exome

AF:

0.773

Gnomad FIN exome

AF:

0.721

Gnomad NFE exome

AF:

0.739

Gnomad OTH exome

AF:

0.752

GnomAD4 exome

AF:

0.754

AC:

1102530

AN:

1461846

Hom.:

417495

Cov.:

AF XY:

0.753

AC XY:

547810

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.960

Gnomad4 AMR exome

AF:

0.789

Gnomad4 ASJ exome

AF:

0.744

Gnomad4 EAS exome

AF:

0.896

Gnomad4 SAS exome

AF:

0.773

Gnomad4 FIN exome

AF:

0.719

Gnomad4 NFE exome

AF:

0.742

Gnomad4 OTH exome

AF:

0.767

GnomAD4 genome

AF:

0.810

AC:

123306

AN:

152184

Hom.:

50618

Cov.:

AF XY:

0.809

AC XY:

60149

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.951

Gnomad4 AMR

AF:

0.782

Gnomad4 ASJ

AF:

0.745

Gnomad4 EAS

AF:

0.905

Gnomad4 SAS

AF:

0.780

Gnomad4 FIN

AF:

0.724

Gnomad4 NFE

AF:

0.743

Gnomad4 OTH

AF:

0.794

Alfa

AF:

0.752

Hom.:

78505

Bravo

AF:

0.818

TwinsUK

AF:

0.731

AC:

2711

ALSPAC

AF:

0.738

AC:

2846

ESP6500AA

AF:

0.943

AC:

3480

ESP6500EA

AF:

0.745

AC:

6092

ExAC

AF:

0.778

AC:

93938

Asia WGS

AF:

0.834

AC:

2898

AN:

3478

EpiCase

AF:

0.741

EpiControl

AF:

0.745

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

8.7

DANN

Benign

0.60

DEOGEN2

Benign

0.0012

T;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.0062

LIST_S2

Benign

0.023

T;T;T

MetaRNN

Benign

7.3e-7

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.8

N;N;.

PrimateAI

Benign

0.36

PROVEAN

Benign

2.5

N;N;N

REVEL

Benign

0.11

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.12

MPC

0.27

ClinPred

0.0024

GERP RS

4.8

Varity_R

0.067

gMVP

0.54

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over