Genetic Variant HOXB2:c.*335C>A (chr17-48542733-G-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_002145.4(HOXB2):c.*335C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 190,770 control chromosomes in the GnomAD database, including 2,678 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 0.16 ( 2080 hom., cov: 32)

Exomes 𝑓: 0.16 ( 598 hom. )

Consequence

HOXB2
NM_002145.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.00

Publications

13 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXB2	NM_002145.4 link	c.*335C>A		3_prime_UTR_variant	Exon 2 of 2	ENST00000330070.6	NP_002136.1	P14652
HOXB2	XM_005257275.5 link	c.*335C>A		3_prime_UTR_variant	Exon 2 of 2		XP_005257332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXB2	ENST00000330070.6 link	c.*335C>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_002145.4	ENSP00000331741.4		P14652
HOXB2	ENST00000504772.3 link	n.192+222C>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23785

AN:

152046

Hom.:

2079

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0812

Gnomad AMI

AF:

0.295

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.183

Gnomad EAS

AF:

0.0859

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.223

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.196

Gnomad OTH

AF:

0.168

GnomAD4 exome

AF:

0.163

AC:

6285

AN:

38606

Hom.:

598

Cov.:

AF XY:

0.163

AC XY:

3221

AN XY:

19728

show subpopulations

African (AFR)

AF:

0.0717

AC:

118

AN:

1646

American (AMR)

AF:

0.137

AC:

170

AN:

1240

Ashkenazi Jewish (ASJ)

AF:

0.170

AC:

290

AN:

1702

East Asian (EAS)

AF:

0.0392

AC:

113

AN:

2882

South Asian (SAS)

AF:

0.120

AC:

AN:

374

European-Finnish (FIN)

AF:

0.205

AC:

377

AN:

1836

Middle Eastern (MID)

AF:

0.205

AC:

AN:

220

European-Non Finnish (NFE)

AF:

0.182

AC:

4739

AN:

26044

Other (OTH)

AF:

0.146

AC:

388

AN:

2662

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

248

495

743

990

1238

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<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:

0.156

AC:

23790

AN:

152164

Hom.:

2080

Cov.:

AF XY:

0.157

AC XY:

11681

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.0813

AC:

3377

AN:

41524

American (AMR)

AF:

0.156

AC:

2385

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.183

AC:

634

AN:

3464

East Asian (EAS)

AF:

0.0855

AC:

444

AN:

5190

South Asian (SAS)

AF:

0.131

AC:

634

AN:

4824

European-Finnish (FIN)

AF:

0.223

AC:

2352

AN:

10568

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.196

AC:

13294

AN:

67982

Other (OTH)

AF:

0.165

AC:

349

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1055

2110

3164

4219

5274

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

256

512

768

1024

1280

<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:

0.175

Hom.:

473

Bravo

AF:

0.148

Asia WGS

AF:

0.131

AC:

454

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over