ENST00000883709.1:c.-70T>C – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000883709.1(HABP2):c.-70T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 1,067,296 control chromosomes in the GnomAD database, including 65,312 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8406 hom., cov: 33)

Exomes 𝑓: 0.34 ( 56906 hom. )

Consequence

HABP2
ENST00000883709.1 5_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.84

Publications

8 publications found

Variant links:

Genes affected

HABP2 (HGNC:4798): (hyaluronan binding protein 2) This gene encodes a member of the peptidase S1 family of serine proteases. The encoded preproprotein is secreted by hepatocytes and proteolytically processed to generate heavy and light chains that form the mature heterodimer. Further autoproteolysis leads to smaller, inactive peptides. This extracellular protease binds hyaluronic acid and may play a role in the coagulation and fibrinolysis systems. Mutations in this gene are associated with nonmedullary thyroid cancer and susceptibility to venous thromboembolism. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

HABP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 10-113553052-T-C is Benign according to our data. Variant chr10-113553052-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 298892.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000883709.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HABP2	NM_001177660.3		c.-10+2091T>C		intron	N/A	NP_001171131.1	Q14520-2
	HABP2	NM_004132.5	MANE Select	c.-70T>C		upstream_gene	N/A	NP_004123.1	Q14520-1

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
HABP2	ENST00000883709.1	c.-70T>C	5_prime_UTR	Exon 1 of 12	ENSP00000553768.1
HABP2	ENST00000883708.1	c.-70T>C	5_prime_UTR	Exon 1 of 12	ENSP00000553767.1
HABP2	ENST00000883710.1	c.-70T>C	5_prime_UTR	Exon 1 of 12	ENSP00000553769.1

Frequencies

GnomAD3 genomes

AF:

0.330

AC:

50035

AN:

151808

Hom.:

8401

Cov.:

show subpopulations

Gnomad AFR

AF:

0.308

Gnomad AMI

AF:

0.371

Gnomad AMR

AF:

0.297

Gnomad ASJ

AF:

0.408

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.467

Gnomad FIN

AF:

0.319

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.346

Gnomad OTH

AF:

0.375

GnomAD4 exome

AF:

0.343

AC:

314105

AN:

915368

Hom.:

56906

Cov.:

AF XY:

0.351

AC XY:

166516

AN XY:

474072

show subpopulations

African (AFR)

AF:

0.308

AC:

6958

AN:

22582

American (AMR)

AF:

0.224

AC:

9055

AN:

40396

Ashkenazi Jewish (ASJ)

AF:

0.407

AC:

8944

AN:

21972

East Asian (EAS)

AF:

0.222

AC:

8185

AN:

36914

South Asian (SAS)

AF:

0.474

AC:

34471

AN:

72760

European-Finnish (FIN)

AF:

0.323

AC:

16971

AN:

52580

Middle Eastern (MID)

AF:

0.485

AC:

2253

AN:

4646

European-Non Finnish (NFE)

AF:

0.342

AC:

212317

AN:

621428

Other (OTH)

AF:

0.355

AC:

14951

AN:

42090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

9886

19771

29657

39542

49428

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4966

9932

14898

19864

24830

<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:

0.330

AC:

50064

AN:

151928

Hom.:

8406

Cov.:

AF XY:

0.331

AC XY:

24575

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.309

AC:

12771

AN:

41378

American (AMR)

AF:

0.296

AC:

4524

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.408

AC:

1418

AN:

3472

East Asian (EAS)

AF:

0.192

AC:

994

AN:

5172

South Asian (SAS)

AF:

0.466

AC:

2247

AN:

4822

European-Finnish (FIN)

AF:

0.319

AC:

3358

AN:

10534

Middle Eastern (MID)

AF:

0.486

AC:

143

AN:

294

European-Non Finnish (NFE)

AF:

0.346

AC:

23488

AN:

67960

Other (OTH)

AF:

0.371

AC:

783

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1761

3522

5282

7043

8804

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

516

1032

1548

2064

2580

<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:

0.336

Hom.:

6274

Bravo

AF:

0.319

Asia WGS

AF:

0.317

AC:

1103

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Factor VII Marburg I Variant Thrombophilia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

6.7

(source)

DANN

Benign

0.80

PhyloP100

-1.8

PromoterAI

-0.023

Neutral

(source)

Mutation Taster

=294/6

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over