chr7-88284046-C-T

Position:

• chr7-88284046-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000380079.9(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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.81 (50618 hom., cov: 31)
  • Exomes 𝑓: 0.75 (417495 hom.)
• Consequence: STEAP4 ENST00000380079.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.753

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]

(HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
STEAP4	NM_024636.4	c.224G>A	p.Gly75Asp	missense_variant	2/5	ENST00000380079.9	NP_078912.2
STEAP4	NM_001205315.2	c.224G>A	p.Gly75Asp	missense_variant	3/6		NP_001192244.1
STEAP4	NM_001205316.2	c.224G>A	p.Gly75Asp	missense_variant	2/4		NP_001192245.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STEAP4	ENST00000380079.9	c.224G>A	p.Gly75Asp	missense_variant	2/5	1	NM_024636.4	ENSP00000369419	P1
	ENST00000628577.2	n.604-8142C>T		intron_variant, non_coding_transcript_variant		5

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

GnomAD3 exomes AF: 0.776 AC: 193402 AN: 249344 Hom.: 75459 AF XY: 0.772 AC XY: 104441 AN XY: 135288

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

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.: 31 AF XY: 0.809 AC XY: 60149 AN XY: 74388

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	T
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	N
LIST_S2	Benign	0.023	T;T;T
MetaRNN	Benign	7.3e-7	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.8	N;N;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.36	T
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	T
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

Other links and lift over

dbSNP: rs1981529; hg19: chr7-87913361;