1-151364974-G-A

Position:

chr1-151364974-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The ENST00000368868.10(SELENBP1):c.1208C>T(p.Thr403Met) variant causes a missense change. The variant allele was found at a frequency of 0.00237 in 1,613,852 control chromosomes in the GnomAD database, including 123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T403K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0014 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 115 hom. )

Consequence

SELENBP1
ENST00000368868.10 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 6.25

Variant links:

Genes affected

SELENBP1 (HGNC:10719): (selenium binding protein 1) This gene encodes a member of the selenium-binding protein family. Selenium is an essential nutrient that exhibits potent anticarcinogenic properties, and deficiency of selenium may cause certain neurologic diseases. The effects of selenium in preventing cancer and neurologic diseases may be mediated by selenium-binding proteins, and decreased expression of this gene may be associated with several types of cancer. The encoded protein may play a selenium-dependent role in ubiquitination/deubiquitination-mediated protein degradation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Apr 2012]

SELENBP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014660746).

BP6

Variant 1-151364974-G-A is Benign according to our data. Variant chr1-151364974-G-A is described in ClinVar as [Benign]. Clinvar id is 3037494.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00137 (208/152220) while in subpopulation SAS AF= 0.0407 (196/4820). AF 95% confidence interval is 0.036. There are 8 homozygotes in gnomad4. There are 159 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SELENBP1	NM_003944.4 linkuse as main transcript	c.1208C>T	p.Thr403Met	missense_variant	11/12	ENST00000368868.10	NP_003935.2
SELENBP1	NM_001258289.2 linkuse as main transcript	c.1334C>T	p.Thr445Met	missense_variant	11/12		NP_001245218.1
SELENBP1	NM_001258288.2 linkuse as main transcript	c.1022C>T	p.Thr341Met	missense_variant	10/11		NP_001245217.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SELENBP1	ENST00000368868.10 linkuse as main transcript	c.1208C>T	p.Thr403Met	missense_variant	11/12	1	NM_003944.4	ENSP00000357861	P1	Q13228-1

Frequencies

GnomAD3 genomes

AF:

0.00137

AC:

209

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0408

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.00503

AC:

1257

AN:

250120

Hom.:

AF XY:

0.00680

AC XY:

919

AN XY:

135108

show subpopulations

Gnomad AFR exome

AF:

0.000372

Gnomad AMR exome

AF:

0.0000871

Gnomad ASJ exome

AF:

0.0000998

Gnomad EAS exome

AF:

0.000327

Gnomad SAS exome

AF:

0.0402

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.00214

GnomAD4 exome

AF:

0.00248

AC:

3622

AN:

1461632

Hom.:

115

Cov.:

AF XY:

0.00355

AC XY:

2579

AN XY:

727090

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0394

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000450

Gnomad4 OTH exome

AF:

0.00238

GnomAD4 genome

AF:

0.00137

AC:

208

AN:

152220

Hom.:

Cov.:

AF XY:

0.00214

AC XY:

159

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0407

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.000235

Hom.:

Bravo

AF:

0.000317

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00574

AC:

697

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SELENBP1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 15, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.37

T;.;.

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

0.98

D;D;D

MetaRNN

Benign

0.015

T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.5

M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-4.0

D;D;.

REVEL

Benign

0.27

Sift

Uncertain

0.015

D;D;.

Sift4G

Uncertain

0.021

D;D;D

Polyphen

0.82

P;.;.

Vest4

0.79

MVP

0.38

MPC

0.37

ClinPred

0.043

GERP RS

4.3

Varity_R

0.15

gMVP

0.74

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over