rs4015375

Variant names:

• chr7-90160861-C-G
• rs4015375
• NM_012449.3:c.141C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-90160861-C-G
• chr7-90160861-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

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. 15/24 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• 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
• Publications: 12 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: Uncertain_significance. The variant received 0 ACMG points.

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.141C>G	p.His47Gln	missense	Exon 3 of 5	NP_036581.1
	STEAP2-AS1	NR_110029.2		n.424+48990G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STEAP1	ENST00000297205.7	TSL:1 MANE Select	c.141C>G	p.His47Gln	missense	Exon 3 of 5	ENSP00000297205.2
	STEAP1	ENST00000475789.1	TSL:1	n.260C>G		non_coding_transcript_exon	Exon 3 of 4
	STEAP1	ENST00000892309.1		c.141C>G	p.His47Gln	missense	Exon 4 of 6	ENSP00000562368.1

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

GnomAD2 exomes AF: 0.00000808 AC: 2 AN: 247402 AF XY: 0.00000748

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000475

Gnomad NFE exome AF: 0.00000898

Gnomad OTH exome AF: 0.00

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000503 AC: 15 AN: 29838

American (AMR) AF: 0.0000229 AC: 1 AN: 43724

Ashkenazi Jewish (ASJ) AF: 0.000203 AC: 5 AN: 24620

East Asian (EAS) AF: 0.00 AC: 0 AN: 39560

South Asian (SAS) AF: 0.0000359 AC: 3 AN: 83630

European-Finnish (FIN) AF: 0.000599 AC: 29 AN: 48454

Middle Eastern (MID) AF: 0.000921 AC: 5 AN: 5426

European-Non Finnish (NFE) AF: 0.000576 AC: 566 AN: 983080

Other (OTH) AF: 0.000531 AC: 29 AN: 54662

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00784 AC: 284 AN: 36212

American (AMR) AF: 0.00465 AC: 66 AN: 14204

Ashkenazi Jewish (ASJ) AF: 0.00126 AC: 4 AN: 3170

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.00219 AC: 10 AN: 4574

European-Finnish (FIN) AF: 0.0139 AC: 123 AN: 8872

Middle Eastern (MID) AF: 0.0188 AC: 5 AN: 266

European-Non Finnish (NFE) AF: 0.00640 AC: 384 AN: 59988

Other (OTH) AF: 0.00683 AC: 13 AN: 1902

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0124 Hom.: 0

ExAC AF: 0.00287 AC: 348

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-0.080
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
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

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