7-90214246-G-T

Variant names:

• chr7-90214246-G-T
• rs194507
• NM_001244944.2:c.-147+2201G>T

Variant summary

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

The NM_001244944.2(STEAP2):​c.-147+2201G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 151,796 control chromosomes in the GnomAD database, including 20,316 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 0.51 (20316 hom., cov: 30)
• Consequence: STEAP2 NM_001244944.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.884
• Publications: 7 publications found

Genes affected

STEAP2 (HGNC:17885): (STEAP2 metalloreductase) This gene is a member of the STEAP family and encodes a multi-pass membrane protein that localizes to the Golgi complex, the plasma membrane, and the vesicular tubular structures in the cytosol. A highly similar protein in mouse has both ferrireductase and cupric reductase activity, and stimulates the cellular uptake of both iron and copper in vitro. Increased transcriptional expression of the human gene is associated with prostate cancer progression. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STEAP2	NM_001244944.2	c.-147+2201G>T		intron_variant	Intron 1 of 5	ENST00000394621.7	NP_001231873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STEAP2	ENST00000394621.7	c.-147+2201G>T		intron_variant	Intron 1 of 5	1	NM_001244944.2	ENSP00000378119.2

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77763 AN: 151676 Hom.: 20296 Cov.: 30

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.513 AC: 77823 AN: 151796 Hom.: 20316 Cov.: 30 AF XY: 0.510 AC XY: 37845 AN XY: 74174

African (AFR) AF: 0.498 AC: 20616 AN: 41386

American (AMR) AF: 0.461 AC: 7033 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1536 AN: 3468

East Asian (EAS) AF: 0.282 AC: 1452 AN: 5142

South Asian (SAS) AF: 0.474 AC: 2274 AN: 4798

European-Finnish (FIN) AF: 0.577 AC: 6085 AN: 10542

Middle Eastern (MID) AF: 0.483 AC: 141 AN: 292

European-Non Finnish (NFE) AF: 0.547 AC: 37135 AN: 67892

Other (OTH) AF: 0.501 AC: 1057 AN: 2108

Alfa AF: 0.529 Hom.: 59104

Bravo AF: 0.501

Asia WGS AF: 0.453 AC: 1578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.7
DANN	Benign	0.59
PhyloP100		0.88
PromoterAI		0.026	Neutral
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: rs194507; hg19: chr7-89843560;