chr7-88282672-C-A

Variant names:

• chr7-88282672-C-A
• rs73205916
• NM_024636.4:c.953G>T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_024636.4(STEAP4):​c.953G>T​(p.Arg318Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00832 in 1,613,856 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0066 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0085 (71 hom.)
• Consequence: STEAP4 NM_024636.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.42

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]

ENSG00000228113 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010172397).
• BP6: Variant 7-88282672-C-A is Benign according to our data. Variant chr7-88282672-C-A is described in ClinVar as [Benign]. Clinvar id is 773216.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STEAP4	NM_024636.4	c.953G>T	p.Arg318Leu	missense_variant	Exon 3 of 5	ENST00000380079.9	NP_078912.2
STEAP4	NM_001205315.2	c.953G>T	p.Arg318Leu	missense_variant	Exon 4 of 6		NP_001192244.1
STEAP4	NM_001205316.2	c.456+1142G>T		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	c.953G>T	p.Arg318Leu	missense_variant	Exon 3 of 5	1	NM_024636.4	ENSP00000369419.4

Frequencies

GnomAD3 genomes AF: 0.00663 AC: 1009 AN: 152110 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00215

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00865

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00660

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0100

Gnomad OTH AF: 0.00527

GnomAD3 exomes AF: 0.00660 AC: 1643 AN: 248840 Hom.: 11 AF XY: 0.00668 AC XY: 901 AN XY: 134978

Gnomad AFR exome AF: 0.00213

Gnomad AMR exome AF: 0.00662

Gnomad ASJ exome AF: 0.00199

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00255

Gnomad FIN exome AF: 0.00726

Gnomad NFE exome AF: 0.00948

Gnomad OTH exome AF: 0.00977

GnomAD4 exome AF: 0.00849 AC: 12416 AN: 1461628 Hom.: 71 Cov.: 31 AF XY: 0.00827 AC XY: 6015 AN XY: 727096

Gnomad4 AFR exome AF: 0.00167

Gnomad4 AMR exome AF: 0.00716

Gnomad4 ASJ exome AF: 0.00210

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00279

Gnomad4 FIN exome AF: 0.00643

Gnomad4 NFE exome AF: 0.00984

Gnomad4 OTH exome AF: 0.00745

GnomAD4 genome AF: 0.00663 AC: 1009 AN: 152228 Hom.: 7 Cov.: 32 AF XY: 0.00626 AC XY: 466 AN XY: 74420

Gnomad4 AFR AF: 0.00214

Gnomad4 AMR AF: 0.00864

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.00660

Gnomad4 NFE AF: 0.0100

Gnomad4 OTH AF: 0.00522

Alfa AF: 0.00773 Hom.: 7

Bravo AF: 0.00652

TwinsUK AF: 0.0140 AC: 52

ALSPAC AF: 0.00960 AC: 37

ESP6500AA AF: 0.00262 AC: 10

ESP6500EA AF: 0.0105 AC: 87

ExAC AF: 0.00678 AC: 819

Asia WGS AF: 0.00115 AC: 5 AN: 3478

EpiCase AF: 0.00834

EpiControl AF: 0.0100

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 30, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.92	D;D
MetaRNN	Benign	0.010	T;T
MetaSVM	Uncertain	0.34	D
MutationAssessor	Pathogenic	3.3	M;.
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-5.5	D;D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		1.0	D;D
Vest4		0.50
MVP		0.95
MPC		0.38
ClinPred		0.039	T
GERP RS		4.3
Varity_R		0.65
gMVP		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs73205916; hg19: chr7-87911987;