Genetic Variant NM_002145.4: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:

Genome browser will be placed here

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over