Variant 2-20641063-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000304031.8(HS1BP3):c.316C>T(p.Arg106Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0062 in 1,614,088 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0046 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0064 ( 45 hom. )

Consequence

HS1BP3
ENST00000304031.8 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.66

Variant links:

Genes affected

HS1BP3 (HGNC:24979): (HCLS1 binding protein 3) The protein encoded by this gene shares similarity with mouse Hs1bp3, an Hcls1/Hs1-interacting protein that may be involved in lymphocyte activation. [provided by RefSeq, Jul 2008]

HS1BP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009174973).

BP6

Variant 2-20641063-G-A is Benign according to our data. Variant chr2-20641063-G-A is described in ClinVar as [Benign]. Clinvar id is 2650705.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HS1BP3	NM_022460.4 linkuse as main transcript	c.316C>T	p.Arg106Trp	missense_variant	3/7	ENST00000304031.8	NP_071905.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HS1BP3	ENST00000304031.8 linkuse as main transcript	c.316C>T	p.Arg106Trp	missense_variant	3/7	1	NM_022460.4	ENSP00000305193	P1

Frequencies

GnomAD3 genomes

AF:

0.00464

AC:

706

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00222

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00995

Gnomad FIN

AF:

0.0153

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00579

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00608

AC:

1529

AN:

251348

Hom.:

AF XY:

0.00684

AC XY:

929

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00179

Gnomad ASJ exome

AF:

0.00288

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0127

Gnomad FIN exome

AF:

0.0125

Gnomad NFE exome

AF:

0.00646

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00636

AC:

9296

AN:

1461772

Hom.:

Cov.:

AF XY:

0.00653

AC XY:

4747

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.000926

Gnomad4 AMR exome

AF:

0.00197

Gnomad4 ASJ exome

AF:

0.00253

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0121

Gnomad4 FIN exome

AF:

0.0123

Gnomad4 NFE exome

AF:

0.00639

Gnomad4 OTH exome

AF:

0.00447

GnomAD4 genome

AF:

0.00464

AC:

707

AN:

152316

Hom.:

Cov.:

AF XY:

0.00497

AC XY:

370

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0102

Gnomad4 FIN

AF:

0.0153

Gnomad4 NFE

AF:

0.00579

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00542

Hom.:

Bravo

AF:

0.00331

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00663

AC:

ExAC

AF:

0.00618

AC:

750

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00556

EpiControl

AF:

0.00646

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

HS1BP3: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.086

T;.;.

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.81

T;T;T

MetaRNN

Benign

0.0092

T;T;T

MetaSVM

Benign

-0.73

MutationAssessor

Benign

1.9

M;.;.

MutationTaster

Benign

0.59

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-4.2

D;D;D

REVEL

Benign

0.26

Sift

Benign

0.054

T;D;D

Sift4G

Uncertain

0.032

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.34

MVP

0.71

MPC

0.60

ClinPred

0.038

GERP RS

4.7

Varity_R

0.16

gMVP

0.59

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over