Variant chr21-43633273-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000291560.7(HSF2BP):c.440G>A(p.Gly147Glu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000162 in 1,611,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

HSF2BP
ENST00000291560.7 missense, splice_region

Scores

Splicing: ADA: 0.8112

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.20

Variant links:

Genes affected

HSF2BP (HGNC:5226): (heat shock transcription factor 2 binding protein) HSF2 binding protein (HSF2BP) associates with HSF2. The interaction occurs between the trimerization domain of HSF2 and the amino terminal hydrophilic region of HSF2BP that comprises two leucine zipper motifs. HSF2BP may therefore be involved in modulating HSF2 activation. [provided by RefSeq, Jul 2008]

HSF2BP links:

HSF2BP (HGNC:):

HSF2BP links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34286904).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSF2BP	NM_007031.2 linkuse as main transcript	c.440G>A	p.Gly147Glu	missense_variant, splice_region_variant	5/9	ENST00000291560.7	NP_008962.1	O75031-1Q6IAT7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSF2BP	ENST00000291560.7 linkuse as main transcript	c.440G>A	p.Gly147Glu	missense_variant, splice_region_variant	5/9	1	NM_007031.2	ENSP00000291560.2		O75031-1
HSF2BP	ENST00000443485.1 linkuse as main transcript	c.440G>A	p.Gly147Glu	missense_variant	5/7	5		ENSP00000409585.1		C9JSF2

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000888

AC:

AN:

247728

Hom.:

AF XY:

0.0000672

AC XY:

AN XY:

133940

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000297

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:

0.000178

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000170

AC:

248

AN:

1458892

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

128

AN XY:

725712

show subpopulations

Gnomad4 AFR exome

AF:

0.0000600

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000220

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000238

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2024

The c.440G>A (p.G147E) alteration is located in exon 5 (coding exon 4) of the HSF2BP gene. This alteration results from a G to A substitution at nucleotide position 440, causing the glycine (G) at amino acid position 147 to be replaced by a glutamic acid (E). 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

0.32

BayesDel_addAF

Benign

-0.067

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

T;T

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.86

D;T

M_CAP

Benign

0.054

MetaRNN

Benign

0.34

T;T

MetaSVM

Benign

-0.50

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-3.1

D;D

REVEL

Benign

0.28

Sift

Uncertain

0.010

D;D

Sift4G

Uncertain

0.017

D;.

Polyphen

0.87

P;.

Vest4

0.71

MVP

0.75

MPC

0.44

ClinPred

0.33

GERP RS

5.0

Varity_R

0.44

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.81

dbscSNV1_RF

Benign

0.33

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