Genetic Variant HOXB2:c.*142C>T (chr17-48542926-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002145.4(HOXB2):c.*142C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 510,568 control chromosomes in the GnomAD database, including 91,279 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.52 ( 22840 hom., cov: 31)

Exomes 𝑓: 0.61 ( 68439 hom. )

Consequence

HOXB2
NM_002145.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.15

Publications

46 publications found

Variant links:

Genes affected

HOXB2 (HGNC:5113): (homeobox B2) This gene is a member of the Antp homeobox family and encodes a nuclear protein with a homeobox DNA-binding domain. It is included in a cluster of homeobox B genes located on chromosome 17. The encoded protein functions as a sequence-specific transcription factor that is involved in development. Increased expression of this gene is associated with pancreatic cancer. [provided by RefSeq, Jul 2008]

HOXB2 links:

HOXB-AS1 (HGNC:43744): (HOXB cluster antisense RNA 1)

HOXB-AS1 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002145.4. 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
	HOXB2	NM_002145.4	MANE Select	c.*142C>T		3_prime_UTR	Exon 2 of 2	NP_002136.1	P14652

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HOXB2	ENST00000330070.6	TSL:1 MANE Select	c.*142C>T	3_prime_UTR	Exon 2 of 2	ENSP00000331741.4	P14652
HOXB2	ENST00000504772.3	TSL:3	n.192+29C>T	intron	N/A
HOXB-AS1	ENST00000717337.1		n.-76G>A	upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.524

AC:

79604

AN:

151868

Hom.:

22819

Cov.:

show subpopulations

Gnomad AFR

AF:

0.264

Gnomad AMI

AF:

0.554

Gnomad AMR

AF:

0.660

Gnomad ASJ

AF:

0.641

Gnomad EAS

AF:

0.668

Gnomad SAS

AF:

0.702

Gnomad FIN

AF:

0.582

Gnomad MID

AF:

0.639

Gnomad NFE

AF:

0.611

Gnomad OTH

AF:

0.568

GnomAD4 exome

AF:

0.611

AC:

218996

AN:

358580

Hom.:

68439

Cov.:

AF XY:

0.614

AC XY:

112312

AN XY:

183052

show subpopulations

African (AFR)

AF:

0.256

AC:

2333

AN:

9108

American (AMR)

AF:

0.692

AC:

7520

AN:

10860

Ashkenazi Jewish (ASJ)

AF:

0.632

AC:

6656

AN:

10524

East Asian (EAS)

AF:

0.722

AC:

17972

AN:

24906

South Asian (SAS)

AF:

0.702

AC:

9396

AN:

13380

European-Finnish (FIN)

AF:

0.588

AC:

21008

AN:

35706

Middle Eastern (MID)

AF:

0.656

AC:

1694

AN:

2582

European-Non Finnish (NFE)

AF:

0.607

AC:

140162

AN:

230866

Other (OTH)

AF:

0.594

AC:

12255

AN:

20648

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

4267

8533

12800

17066

21333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1432

2864

4296

5728

7160

<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:

0.524

AC:

79651

AN:

151988

Hom.:

22840

Cov.:

AF XY:

0.529

AC XY:

39312

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.264

AC:

10946

AN:

41440

American (AMR)

AF:

0.661

AC:

10097

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.641

AC:

2225

AN:

3472

East Asian (EAS)

AF:

0.668

AC:

3451

AN:

5166

South Asian (SAS)

AF:

0.701

AC:

3375

AN:

4812

European-Finnish (FIN)

AF:

0.582

AC:

6145

AN:

10554

Middle Eastern (MID)

AF:

0.650

AC:

191

AN:

294

European-Non Finnish (NFE)

AF:

0.611

AC:

41515

AN:

67956

Other (OTH)

AF:

0.571

AC:

1203

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1768

3535

5303

7070

8838

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

700

1400

2100

2800

3500

<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:

0.587

Hom.:

47100

Bravo

AF:

0.516

Asia WGS

AF:

0.665

AC:

2315

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

1.1

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over