rs4015375

Positions:

• chr7-90160861-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012449.3(STEAP1):​c.141C>G​(p.His47Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,448,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00050 (0 hom.)
• Consequence: STEAP1 NM_012449.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STEAP1	NM_012449.3	c.141C>G	p.His47Gln	missense_variant	3/5	ENST00000297205.7
STEAP2-AS1	NR_110029.2	n.424+48990G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STEAP1	ENST00000297205.7	c.141C>G	p.His47Gln	missense_variant	3/5	1	NM_012449.3	P1
STEAP1	ENST00000475789.1	n.260C>G		non_coding_transcript_exon_variant	3/4	1
STEAP2-AS1	ENST00000478318.6	n.424+48990G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00662 AC: 893 AN: 134982 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00784

Gnomad AMI AF: 0.00531

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.00126

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00218

Gnomad FIN AF: 0.0139

Gnomad MID AF: 0.0211

Gnomad NFE AF: 0.00640

Gnomad OTH AF: 0.00691

GnomAD4 exome AF: 0.000497 AC: 653 AN: 1312994 Hom.: 0 Cov.: 31 AF XY: 0.000474 AC XY: 311 AN XY: 656618

Gnomad4 AFR exome AF: 0.000503

Gnomad4 AMR exome AF: 0.0000229

Gnomad4 ASJ exome AF: 0.000203

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000359

Gnomad4 FIN exome AF: 0.000599

Gnomad4 NFE exome AF: 0.000576

Gnomad4 OTH exome AF: 0.000531

GnomAD4 genome AF: 0.00661 AC: 893 AN: 135084 Hom.: 0 Cov.: 31 AF XY: 0.00683 AC XY: 452 AN XY: 66150

Gnomad4 AFR AF: 0.00784

Gnomad4 AMR AF: 0.00465

Gnomad4 ASJ AF: 0.00126

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00219

Gnomad4 FIN AF: 0.0139

Gnomad4 NFE AF: 0.00640

Gnomad4 OTH AF: 0.00683

Alfa AF: 0.0124 Hom.: 0

ExAC AF: 0.00287 AC: 348

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Benign	0.58
DEOGEN2	Benign	0.051	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.0076	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.10
Sift	Benign	0.46	T
Sift4G	Benign	0.55	T
Polyphen		0.0	B
Vest4		0.076
MutPred		0.096		Gain of helix (P = 0.132);
MVP		0.29
MPC		0.046
ClinPred		0.032	T
GERP RS		-2.3
Varity_R		0.033
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.32		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4015375; hg19: chr7-89790175; COSMIC: COSV51880898; COSMIC: COSV51880898;