7-88276856-T-C

Position:

• chr7-88276856-T-C

Variant summary

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

The NM_024636.4(STEAP4):​c.*2542A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 152,276 control chromosomes in the GnomAD database, including 24,042 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 0.56 (24008 hom., cov: 32)
  • Exomes 𝑓: 0.53 (34 hom.)
• Consequence: STEAP4 NM_024636.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STEAP4	NM_024636.4	c.*2542A>G		3_prime_UTR_variant	5/5	ENST00000380079.9	NP_078912.2
STEAP4	NM_001205315.2	c.*2542A>G		3_prime_UTR_variant	6/6		NP_001192244.1
STEAP4	NM_001205316.2	c.*2542A>G		3_prime_UTR_variant	4/4		NP_001192245.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STEAP4	ENST00000380079.9	c.*2542A>G		3_prime_UTR_variant	5/5	1	NM_024636.4	ENSP00000369419.4

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84398 AN: 151888 Hom.: 23996 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.836

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.561

GnomAD4 exome AF: 0.530 AC: 143 AN: 270 Hom.: 34 Cov.: 0 AF XY: 0.532 AC XY: 66 AN XY: 124

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.875

Gnomad4 FIN exome AF: 0.484

Gnomad4 NFE exome AF: 0.552

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.556 AC: 84449 AN: 152006 Hom.: 24008 Cov.: 32 AF XY: 0.555 AC XY: 41256 AN XY: 74276

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.619

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.836

Gnomad4 SAS AF: 0.653

Gnomad4 FIN AF: 0.525

Gnomad4 NFE AF: 0.581

Gnomad4 OTH AF: 0.559

Alfa AF: 0.575 Hom.: 32796

Bravo AF: 0.558

Asia WGS AF: 0.710 AC: 2467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.77

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: rs8122; hg19: chr7-87906171;