rs772995703

Variant names:

• chr7-88280924-T-A
• rs772995703
• NM_024636.4:c.1140A>T

Your query was ambiguous. Multiple possible variants found:

• chr7-88280924-T-A
• chr7-88280924-T-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_024636.4(STEAP4):​c.1140A>T​(p.Arg380Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000274 in 1,604,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: STEAP4 NM_024636.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.10
• Publications: 0 publications found

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]

SRI-AS1 (HGNC:40564): (SRI antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 7-88280924-T-A is Benign according to our data. Variant chr7-88280924-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 722292.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=3.1 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024636.4. 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
	STEAP4	NM_024636.4	MANE Select	c.1140A>T	p.Arg380Arg	synonymous	Exon 4 of 5	NP_078912.2	Q687X5-1
	STEAP4	NM_001205315.2		c.1140A>T	p.Arg380Arg	synonymous	Exon 5 of 6	NP_001192244.1	Q687X5-1
	STEAP4	NM_001205316.2		c.612A>T	p.Arg204Arg	synonymous	Exon 3 of 4	NP_001192245.1	Q687X5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STEAP4	ENST00000380079.9	TSL:1 MANE Select	c.1140A>T	p.Arg380Arg	synonymous	Exon 4 of 5	ENSP00000369419.4	Q687X5-1
	STEAP4	ENST00000301959.9	TSL:1	c.612A>T	p.Arg204Arg	synonymous	Exon 3 of 4	ENSP00000305545.5	Q687X5-2
	STEAP4	ENST00000879105.1		c.1140A>T	p.Arg380Arg	synonymous	Exon 5 of 6	ENSP00000549164.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152112 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000209 AC: 5 AN: 239328 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000158

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000296 AC: 43 AN: 1452206 Hom.: 0 Cov.: 30 AF XY: 0.0000263 AC XY: 19 AN XY: 722544

African (AFR) AF: 0.00 AC: 0 AN: 32776

American (AMR) AF: 0.000141 AC: 6 AN: 42692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25812

East Asian (EAS) AF: 0.00 AC: 0 AN: 38974

South Asian (SAS) AF: 0.00 AC: 0 AN: 84518

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.0000316 AC: 35 AN: 1108448

Other (OTH) AF: 0.0000333 AC: 2 AN: 59984

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152112 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74294

African (AFR) AF: 0.00 AC: 0 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2090

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	7.9
DANN	Benign	0.87
PhyloP100		3.1

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: rs772995703; hg19: chr7-87910239;