rs61737475

Variant names:

• chr7-90164518-C-T
• rs61737475
• NM_012449.3:c.804C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-90164518-C-T
• chr7-90164518-C-A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.216
• Publications: 2 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012449.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STEAP1	NM_012449.3	MANE Select	c.804C>T	p.His268His	synonymous	Exon 5 of 5	NP_036581.1	Q9UHE8
	STEAP2-AS1	NR_110029.2		n.424+45333G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STEAP1	ENST00000297205.7	TSL:1 MANE Select	c.804C>T	p.His268His	synonymous	Exon 5 of 5	ENSP00000297205.2	Q9UHE8
	STEAP1	ENST00000892309.1		c.804C>T	p.His268His	synonymous	Exon 6 of 6	ENSP00000562368.1
	STEAP1	ENST00000927746.1		c.804C>T	p.His268His	synonymous	Exon 6 of 6	ENSP00000597805.1

Frequencies

GnomAD3 genomes AF: 0.00465 AC: 707 AN: 152098 Hom.: 4 Cov.: 33

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

GnomAD2 exomes AF: 0.00463 AC: 1160 AN: 250680 AF XY: 0.00472

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 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.: 27 Cov.: 31 AF XY: 0.00598 AC XY: 4343 AN XY: 726694

African (AFR) AF: 0.00164 AC: 55 AN: 33448

American (AMR) AF: 0.00184 AC: 82 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.00211 AC: 55 AN: 26108

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39624

South Asian (SAS) AF: 0.00179 AC: 154 AN: 86126

European-Finnish (FIN) AF: 0.00415 AC: 221 AN: 53280

Middle Eastern (MID) AF: 0.00417 AC: 24 AN: 5762

European-Non Finnish (NFE) AF: 0.00710 AC: 7888 AN: 1111548

Other (OTH) AF: 0.00550 AC: 332 AN: 60356

GnomAD4 genome AF: 0.00464 AC: 706 AN: 152216 Hom.: 4 Cov.: 33 AF XY: 0.00433 AC XY: 322 AN XY: 74424

African (AFR) AF: 0.00231 AC: 96 AN: 41528

American (AMR) AF: 0.00281 AC: 43 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4824

European-Finnish (FIN) AF: 0.00264 AC: 28 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00769 AC: 523 AN: 67996

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00622 Hom.: 0

Bravo AF: 0.00453

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00787

EpiControl AF: 0.00848

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	STEAP1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	8.7
DANN	Benign	0.59
PhyloP100		-0.22
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs61737475; hg19: chr7-89793832;