chr7-88282672-C-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 773216.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024636.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STEAP4	NM_024636.4	MANE Select	c.953G>T	p.Arg318Leu	missense	Exon 3 of 5	NP_078912.2	Q687X5-1
	STEAP4	NM_001205315.2		c.953G>T	p.Arg318Leu	missense	Exon 4 of 6	NP_001192244.1	Q687X5-1
	STEAP4	NM_001205316.2		c.456+1142G>T		intron	N/A	NP_001192245.1	Q687X5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STEAP4	ENST00000380079.9	TSL:1 MANE Select	c.953G>T	p.Arg318Leu	missense	Exon 3 of 5	ENSP00000369419.4	Q687X5-1
	STEAP4	ENST00000301959.9	TSL:1	c.456+1142G>T		intron	N/A	ENSP00000305545.5	Q687X5-2
	STEAP4	ENST00000879105.1		c.953G>T	p.Arg318Leu	missense	Exon 4 of 6	ENSP00000549164.1

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

GnomAD2 exomes AF: 0.00660 AC: 1643 AN: 248840 AF XY: 0.00668

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 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

African (AFR) AF: 0.00167 AC: 56 AN: 33472

American (AMR) AF: 0.00716 AC: 320 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00210 AC: 55 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00279 AC: 241 AN: 86238

European-Finnish (FIN) AF: 0.00643 AC: 343 AN: 53368

Middle Eastern (MID) AF: 0.00226 AC: 13 AN: 5764

European-Non Finnish (NFE) AF: 0.00984 AC: 10938 AN: 1111882

Other (OTH) AF: 0.00745 AC: 450 AN: 60386

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

African (AFR) AF: 0.00214 AC: 89 AN: 41542

American (AMR) AF: 0.00864 AC: 132 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4824

European-Finnish (FIN) AF: 0.00660 AC: 70 AN: 10608

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0100 AC: 681 AN: 68008

Other (OTH) AF: 0.00522 AC: 11 AN: 2108

Alfa AF: 0.00771 Hom.: 20

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.92	D
MetaRNN	Benign	0.010	T
MetaSVM	Uncertain	0.34	D
MutationAssessor	Pathogenic	3.3	M
PhyloP100		3.4
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	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
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs73205916; hg19: chr7-87911987; COSMIC: COSV108123734; COSMIC: COSV108123734;