rs2040657

Positions:

• chr7-88285865-A-T

Variant summary

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

The NM_024636.4(STEAP4):​c.-2-1594T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0434 in 152,224 control chromosomes in the GnomAD database, including 177 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.043 (177 hom., cov: 32)
• Consequence: STEAP4 NM_024636.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.480

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 (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STEAP4	NM_024636.4	c.-2-1594T>A		intron_variant		ENST00000380079.9
STEAP4	NM_001205315.2	c.-2-1594T>A		intron_variant
STEAP4	NM_001205316.2	c.-2-1594T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STEAP4	ENST00000380079.9	c.-2-1594T>A		intron_variant		1	NM_024636.4	P1
	ENST00000628577.2	n.604-6323A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0435 AC: 6612 AN: 152108 Hom.: 178 Cov.: 32

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0623

Gnomad ASJ AF: 0.0645

Gnomad EAS AF: 0.0594

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0376

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0531

Gnomad OTH AF: 0.0544

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0434 AC: 6601 AN: 152224 Hom.: 177 Cov.: 32 AF XY: 0.0448 AC XY: 3332 AN XY: 74432

Gnomad4 AFR AF: 0.0109

Gnomad4 AMR AF: 0.0621

Gnomad4 ASJ AF: 0.0645

Gnomad4 EAS AF: 0.0588

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.0376

Gnomad4 NFE AF: 0.0532

Gnomad4 OTH AF: 0.0539

Alfa AF: 0.0451 Hom.: 25

Bravo AF: 0.0424

Asia WGS AF: 0.0620 AC: 217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.6
DANN	Benign	0.64

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: rs2040657; hg19: chr7-87915180;