dbSNP rs144007277: STEAP1B:p.Phe68Val (chr7-22493719-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001382447.1(STEAP1B):c.202T>G(p.Phe68Val) variant causes a missense change. The variant allele was found at a frequency of 0.00208 in 1,613,986 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.011 ( 27 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 41 hom. )

Consequence

STEAP1B
NM_001382447.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.04

Variant links:

Genes affected

STEAP1B (HGNC:41907): (STEAP family member 1B) Predicted to be integral component of membrane. Predicted to be active in endosome and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

STEAP1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009422809).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0108 (1651/152336) while in subpopulation AFR AF= 0.0379 (1577/41568). AF 95% confidence interval is 0.0364. There are 27 homozygotes in gnomad4. There are 774 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STEAP1B	NM_001382447.1 link	c.202T>G	p.Phe68Val	missense_variant	Exon 3 of 5	ENST00000678116.1	NP_001369376.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STEAP1B	ENST00000678116.1 link	c.202T>G	p.Phe68Val	missense_variant	Exon 3 of 5		NM_001382447.1	ENSP00000503251.1		A0A7I2V339

Frequencies

GnomAD3 genomes

AF:

0.0107

AC:

1636

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0377

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00340

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00277

AC:

695

AN:

251166

Hom.:

AF XY:

0.00211

AC XY:

286

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.0394

Gnomad AMR exome

AF:

0.00130

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.00117

AC:

1709

AN:

1461650

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

739

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.0439

Gnomad4 AMR exome

AF:

0.00136

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.00255

GnomAD4 genome

AF:

0.0108

AC:

1651

AN:

152336

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

774

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0379

Gnomad4 AMR

AF:

0.00340

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.000497

Hom.:

Bravo

AF:

0.0122

ESP6500AA

AF:

0.0419

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00341

AC:

414

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.63

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.31

T;.;T;T

Eigen

Uncertain

0.19

Eigen_PC

Benign

-0.014

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.81

T;T;T;T

MetaRNN

Benign

0.0094

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.3

M;.;.;.

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-5.8

D;D;D;D

REVEL

Benign

0.10

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Uncertain

0.0050

D;D;D;.

Polyphen

0.94

P;.;.;.

Vest4

0.70

MVP

0.048

MPC

0.74

ClinPred

0.10

GERP RS

1.1

Varity_R

0.46

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over