rs116270469

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_024636.4(STEAP4):c.830G>A(p.Arg277His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,614,106 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 7 hom., cov: 32)

Exomes 𝑓: 0.00062 ( 8 hom. )

Consequence

STEAP4
NM_024636.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.550

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0075223744).

BP6

Variant 7-88282795-C-T is Benign according to our data. Variant chr7-88282795-C-T is described in ClinVar as [Benign]. Clinvar id is 790602.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00507 (772/152244) while in subpopulation AFR AF= 0.0173 (717/41532). AF 95% confidence interval is 0.0162. There are 7 homozygotes in gnomad4. There are 344 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
STEAP4	NM_024636.4 link	c.830G>A	p.Arg277His	missense_variant	Exon 3 of 5	ENST00000380079.9	NP_078912.2
STEAP4	NM_001205315.2 link	c.830G>A	p.Arg277His	missense_variant	Exon 4 of 6		NP_001192244.1
STEAP4	NM_001205316.2 link	c.456+1019G>A		intron_variant	Intron 2 of 3		NP_001192245.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STEAP4	ENST00000380079.9 link	c.830G>A	p.Arg277His	missense_variant	Exon 3 of 5	1	NM_024636.4	ENSP00000369419.4		Q687X5-1

Frequencies

GnomAD3 genomes

AF:

0.00509

AC:

774

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0173

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00137

AC:

341

AN:

249426

Hom.:

AF XY:

0.00110

AC XY:

149

AN XY:

135314

show subpopulations

Gnomad AFR exome

AF:

0.0191

Gnomad AMR exome

AF:

0.000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.000622

AC:

909

AN:

1461862

Hom.:

Cov.:

AF XY:

0.000572

AC XY:

416

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.0185

Gnomad4 AMR exome

AF:

0.000828

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000378

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000147

Gnomad4 OTH exome

AF:

0.00114

GnomAD4 genome

AF:

0.00507

AC:

772

AN:

152244

Hom.:

Cov.:

AF XY:

0.00462

AC XY:

344

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0173

Gnomad4 AMR

AF:

0.00236

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000945

Hom.:

Bravo

AF:

0.00572

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0145

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00166

AC:

201

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 16, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

T;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.88

D;D

MetaRNN

Benign

0.0075

T;T

MetaSVM

Uncertain

-0.029

MutationAssessor

Benign

1.8

L;.

PrimateAI

Benign

0.20

PROVEAN

Uncertain

-3.0

D;D

REVEL

Benign

0.29

Sift

Benign

0.030

D;D

Sift4G

Uncertain

0.0080

D;D

Polyphen

0.058

B;B

Vest4

0.10

MVP

0.83

MPC

0.26

ClinPred

0.024

GERP RS

4.0

Varity_R

0.22

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over