Genetic Variant NM_012449.3:c.804C>T (chr7-90164518-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_012449.3(STEAP1):c.804C>T(p.His268His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0059 in 1,613,138 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0060 ( 27 hom. )

Consequence

STEAP1
NM_012449.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.216

Variant links:

Genes affected

STEAP1 (HGNC:11378): (STEAP family member 1) This gene is predominantly expressed in prostate tissue, and is found to be upregulated in multiple cancer cell lines. The gene product is predicted to be a six-transmembrane protein, and was shown to be a cell surface antigen significantly expressed at cell-cell junctions. [provided by RefSeq, Jul 2008]

STEAP1 links:

STEAP2-AS1 (HGNC:40820): (STEAP2 antisense RNA 1)

STEAP2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 7-90164518-C-T is Benign according to our data. Variant chr7-90164518-C-T is described in ClinVar as [Benign]. Clinvar id is 770940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.216 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STEAP1	NM_012449.3 link	c.804C>T	p.His268His	synonymous_variant	Exon 5 of 5	ENST00000297205.7	NP_036581.1	Q9UHE8
STEAP2-AS1	NR_110029.2 link	n.424+45333G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
STEAP1	ENST00000297205.7 link	c.804C>T	p.His268His	synonymous_variant	Exon 5 of 5	1	NM_012449.3	ENSP00000297205.2	Q9UHE8
STEAP1	ENST00000412573.1 link	n.*92C>T		non_coding_transcript_exon_variant	Exon 4 of 4	3		ENSP00000394402.1	H7C0D8
STEAP1	ENST00000412573.1 link	n.*92C>T		3_prime_UTR_variant	Exon 4 of 4	3		ENSP00000394402.1	H7C0D8
STEAP2-AS1	ENST00000478318.6 link	n.424+45333G>A		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.00465

AC:

707

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00234

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00282

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00264

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00769

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00463

AC:

1160

AN:

250680

Hom.:

AF XY:

0.00472

AC XY:

640

AN XY:

135492

show subpopulations

Gnomad AFR exome

AF:

0.00203

Gnomad AMR exome

AF:

0.00189

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00177

Gnomad FIN exome

AF:

0.00391

Gnomad NFE exome

AF:

0.00783

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.00603

AC:

8813

AN:

1460922

Hom.:

Cov.:

AF XY:

0.00598

AC XY:

4343

AN XY:

726694

show subpopulations

Gnomad4 AFR exome

AF:

0.00164

Gnomad4 AMR exome

AF:

0.00184

Gnomad4 ASJ exome

AF:

0.00211

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00179

Gnomad4 FIN exome

AF:

0.00415

Gnomad4 NFE exome

AF:

0.00710

Gnomad4 OTH exome

AF:

0.00550

GnomAD4 genome

AF:

0.00464

AC:

706

AN:

152216

Hom.:

Cov.:

AF XY:

0.00433

AC XY:

322

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.00231

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00264

Gnomad4 NFE

AF:

0.00769

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00622

Hom.:

Bravo

AF:

0.00453

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00787

EpiControl

AF:

0.00848

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 04, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

STEAP1-related disorder

Benign:1

Jun 18, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

8.7

DANN

Benign

0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over