Variant 2-20624845-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The ENST00000304031.8(HS1BP3):c.671C>T(p.Pro224Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00181 in 1,613,834 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00093 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 6 hom. )

Consequence

HS1BP3
ENST00000304031.8 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 3.78

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017283529).

BP6

Variant 2-20624845-G-A is Benign according to our data. Variant chr2-20624845-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 808674.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=2}.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HS1BP3	NM_022460.4 linkuse as main transcript	c.671C>T	p.Pro224Leu	missense_variant	5/7	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.671C>T	p.Pro224Leu	missense_variant	5/7	1	NM_022460.4	ENSP00000305193	P1

Frequencies

GnomAD3 genomes

AF:

0.000926

AC:

141

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00181

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00104

AC:

262

AN:

251152

Hom.:

AF XY:

0.00113

AC XY:

154

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000522

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00207

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.00191

AC:

2785

AN:

1461504

Hom.:

Cov.:

AF XY:

0.00182

AC XY:

1324

AN XY:

727080

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.000605

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000939

Gnomad4 NFE exome

AF:

0.00241

Gnomad4 OTH exome

AF:

0.000927

GnomAD4 genome

AF:

0.000926

AC:

141

AN:

152330

Hom.:

Cov.:

AF XY:

0.000698

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00181

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00175

Hom.:

Bravo

AF:

0.00103

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00244

AC:

ExAC

AF:

0.00133

AC:

161

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00294

EpiControl

AF:

0.00213

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	HS1BP3: BP4 -
Uncertain significance, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2021

The c.671C>T (p.P224L) alteration is located in exon 5 (coding exon 5) of the HS1BP3 gene. This alteration results from a C to T substitution at nucleotide position 671, causing the proline (P) at amino acid position 224 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.056

.;T;T

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.84

T;T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.017

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.9

.;L;.

MutationTaster

Benign

0.96

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.0

.;D;D

REVEL

Benign

0.13

Sift

Uncertain

0.011

.;D;D

Sift4G

Uncertain

0.010

.;D;D

Polyphen

0.93

.;P;.

Vest4

0.40

MVP

0.62

MPC

0.52

ClinPred

0.055

GERP RS

4.7

Varity_R

0.062

gMVP

0.19

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