Genetic Variant HS1BP3:p.Ala388Thr (chr2-20619004-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022460.4(HS1BP3):c.1162G>A(p.Ala388Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 1,613,200 control chromosomes in the GnomAD database, including 34,443 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 2578 hom., cov: 33)

Exomes 𝑓: 0.21 ( 31865 hom. )

Consequence

HS1BP3
NM_022460.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.54

Publications

21 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036723316).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
HS1BP3	NM_022460.4 link	c.1162G>A	p.Ala388Thr	missense_variant	Exon 7 of 7	ENST00000304031.8	NP_071905.3
HS1BP3	XM_017004696.3 link	c.920+4892G>A		intron_variant	Intron 6 of 7		XP_016860185.1
HS1BP3	XM_017004697.3 link	c.920+4892G>A		intron_variant	Intron 6 of 7		XP_016860186.1
HS1BP3	XM_017004698.2 link	c.920+4892G>A		intron_variant	Intron 6 of 7		XP_016860187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HS1BP3	ENST00000304031.8 link	c.1162G>A	p.Ala388Thr	missense_variant	Exon 7 of 7	1	NM_022460.4	ENSP00000305193.3

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26777

AN:

151976

Hom.:

2575

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.375

Gnomad AMR

AF:

0.142

Gnomad ASJ

AF:

0.189

Gnomad EAS

AF:

0.0847

Gnomad SAS

AF:

0.190

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.213

Gnomad OTH

AF:

0.173

GnomAD2 exomes

AF:

0.183

AC:

45529

AN:

249440

AF XY:

0.186

show subpopulations

Gnomad AFR exome

AF:

0.132

Gnomad AMR exome

AF:

0.141

Gnomad ASJ exome

AF:

0.184

Gnomad EAS exome

AF:

0.0894

Gnomad FIN exome

AF:

0.180

Gnomad NFE exome

AF:

0.212

Gnomad OTH exome

AF:

0.181

GnomAD4 exome

AF:

0.205

AC:

299923

AN:

1461106

Hom.:

31865

Cov.:

AF XY:

0.206

AC XY:

149866

AN XY:

726854

show subpopulations

African (AFR)

AF:

0.134

AC:

4487

AN:

33474

American (AMR)

AF:

0.142

AC:

6324

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.188

AC:

4897

AN:

26090

East Asian (EAS)

AF:

0.0836

AC:

3318

AN:

39698

South Asian (SAS)

AF:

0.202

AC:

17444

AN:

86174

European-Finnish (FIN)

AF:

0.180

AC:

9615

AN:

53278

Middle Eastern (MID)

AF:

0.175

AC:

1011

AN:

5762

European-Non Finnish (NFE)

AF:

0.217

AC:

241419

AN:

1111608

Other (OTH)

AF:

0.189

AC:

11408

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

12846

25692

38538

51384

64230

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8334

16668

25002

33336

41670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.176

AC:

26779

AN:

152094

Hom.:

2578

Cov.:

AF XY:

0.175

AC XY:

13011

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.132

AC:

5493

AN:

41490

American (AMR)

AF:

0.142

AC:

2171

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.189

AC:

655

AN:

3468

East Asian (EAS)

AF:

0.0845

AC:

436

AN:

5158

South Asian (SAS)

AF:

0.190

AC:

914

AN:

4816

European-Finnish (FIN)

AF:

0.179

AC:

1896

AN:

10592

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.213

AC:

14454

AN:

67950

Other (OTH)

AF:

0.172

AC:

363

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1126

2252

3378

4504

5630

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

288

576

864

1152

1440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.195

Hom.:

6780

Bravo

AF:

0.171

TwinsUK

AF:

0.221

AC:

820

ALSPAC

AF:

0.221

AC:

852

ESP6500AA

AF:

0.139

AC:

611

ESP6500EA

AF:

0.208

AC:

1793

ExAC

AF:

0.183

AC:

22176

Asia WGS

AF:

0.129

AC:

448

AN:

3478

EpiCase

AF:

0.214

EpiControl

AF:

0.213

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.015

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.0016

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.46

MetaRNN

Benign

0.0037

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.48

PhyloP100

-1.5

PrimateAI

Benign

0.30

PROVEAN

Benign

0.020

REVEL

Benign

0.043

Sift

Benign

0.65

Sift4G

Benign

0.20

Polyphen

0.0080

Vest4

0.0050

MPC

0.13

ClinPred

0.00059

GERP RS

-1.7

Varity_R

0.029

gMVP

0.090

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over