7-88284046-C-T

Variant names:

• chr7-88284046-C-T
• rs1981529
• NM_024636.4:c.224G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.81 (50618 hom., cov: 31)
  • Exomes 𝑓: 0.75 (417495 hom.)
• Consequence: STEAP4 NM_024636.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.753
• Publications: 50 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 -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.

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.224G>A	p.Gly75Asp	missense	Exon 2 of 5	NP_078912.2
	STEAP4	NM_001205315.2		c.224G>A	p.Gly75Asp	missense	Exon 3 of 6	NP_001192244.1
	STEAP4	NM_001205316.2		c.224G>A	p.Gly75Asp	missense	Exon 2 of 4	NP_001192245.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STEAP4	ENST00000380079.9	TSL:1 MANE Select	c.224G>A	p.Gly75Asp	missense	Exon 2 of 5	ENSP00000369419.4
	STEAP4	ENST00000301959.9	TSL:1	c.224G>A	p.Gly75Asp	missense	Exon 2 of 4	ENSP00000305545.5
	STEAP4	ENST00000879105.1		c.224G>A	p.Gly75Asp	missense	Exon 3 of 6	ENSP00000549164.1

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123196 AN: 152066 Hom.: 50562 Cov.: 31

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

GnomAD2 exomes AF: 0.776 AC: 193402 AN: 249344 AF XY: 0.772

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 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.: 73 AF XY: 0.753 AC XY: 547810 AN XY: 727220

African (AFR) AF: 0.960 AC: 32128 AN: 33480

American (AMR) AF: 0.789 AC: 35289 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 19456 AN: 26136

East Asian (EAS) AF: 0.896 AC: 35551 AN: 39696

South Asian (SAS) AF: 0.773 AC: 66661 AN: 86256

European-Finnish (FIN) AF: 0.719 AC: 38429 AN: 53416

Middle Eastern (MID) AF: 0.713 AC: 4109 AN: 5762

European-Non Finnish (NFE) AF: 0.742 AC: 824595 AN: 1111996

Other (OTH) AF: 0.767 AC: 46312 AN: 60396

GnomAD4 genome AF: 0.810 AC: 123306 AN: 152184 Hom.: 50618 Cov.: 31 AF XY: 0.809 AC XY: 60149 AN XY: 74388

African (AFR) AF: 0.951 AC: 39527 AN: 41548

American (AMR) AF: 0.782 AC: 11944 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 2588 AN: 3472

East Asian (EAS) AF: 0.905 AC: 4688 AN: 5180

South Asian (SAS) AF: 0.780 AC: 3758 AN: 4820

European-Finnish (FIN) AF: 0.724 AC: 7661 AN: 10580

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.743 AC: 50521 AN: 67984

Other (OTH) AF: 0.794 AC: 1677 AN: 2112

Alfa AF: 0.762 Hom.: 118866

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.7
DANN	Benign	0.60
DEOGEN2	Benign	0.0012	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.0062	N
LIST_S2	Benign	0.023	T
MetaRNN	Benign	7.3e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.8	N
PhyloP100		0.75
PrimateAI	Benign	0.36	T
PROVEAN	Benign	2.5	N
REVEL	Benign	0.11
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.12
MPC		0.27
ClinPred		0.0024	T
GERP RS		4.8
Varity_R		0.067
gMVP		0.54
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1981529; hg19: chr7-87913361; COSMIC: COSV107387083;