Genetic Variant HOXB5:c.*141G>A (chr17-48592068-C-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_002147.4(HOXB5):c.*141G>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 0.609 in 884,580 control chromosomes in the GnomAD database, including 169,944 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 ( 23204 hom., cov: 28)

Exomes 𝑓: 0.63 ( 146740 hom. )

Consequence

HOXB5
NM_002147.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.03

Publications

85 publications found

Variant links:

Genes affected

HOXB5 (HGNC:5116): (homeobox B5) 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 lung and gut development. Increased expression of this gene is associated with a distinct biologic subset of acute myeloid leukemia (AML) and the occurrence of bronchopulmonary sequestration (BPS) and congenital cystic adenomatoid malformation (CCAM) tissue. [provided by RefSeq, Jul 2008]

HOXB5 links:

HOXB-AS3 (HGNC:40283): (HOXB cluster antisense RNA 3)

HOXB-AS3 links:

HOXB3 (HGNC:5114): (homeobox B3) 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 a distinct biologic subset of acute myeloid leukemia (AML). [provided by RefSeq, Jul 2008]

HOXB3 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=-0.22).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXB5	NM_002147.4 link	c.*141G>A		3_prime_UTR_variant	Exon 2 of 2	ENST00000239151.6	NP_002138.1	P09067

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXB5	ENST00000239151.6 link	c.*141G>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_002147.4	ENSP00000239151.4		P09067

Frequencies

GnomAD3 genomes

AF:

0.522

AC:

79038

AN:

151284

Hom.:

23199

Cov.:

show subpopulations

Gnomad AFR

AF:

0.229

Gnomad AMI

AF:

0.576

Gnomad AMR

AF:

0.585

Gnomad ASJ

AF:

0.570

Gnomad EAS

AF:

0.538

Gnomad SAS

AF:

0.582

Gnomad FIN

AF:

0.700

Gnomad MID

AF:

0.567

Gnomad NFE

AF:

0.649

Gnomad OTH

AF:

0.552

GnomAD4 exome

AF:

0.627

AC:

459452

AN:

733180

Hom.:

146740

Cov.:

AF XY:

0.628

AC XY:

234515

AN XY:

373676

show subpopulations

African (AFR)

AF:

0.219

AC:

4012

AN:

18290

American (AMR)

AF:

0.594

AC:

12344

AN:

20776

Ashkenazi Jewish (ASJ)

AF:

0.565

AC:

8785

AN:

15550

East Asian (EAS)

AF:

0.565

AC:

18765

AN:

33218

South Asian (SAS)

AF:

0.598

AC:

32206

AN:

53816

European-Finnish (FIN)

AF:

0.690

AC:

22022

AN:

31900

Middle Eastern (MID)

AF:

0.610

AC:

1515

AN:

2482

European-Non Finnish (NFE)

AF:

0.649

AC:

338534

AN:

521586

Other (OTH)

AF:

0.598

AC:

21269

AN:

35562

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

8020

16040

24059

32079

40099

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.522

AC:

79059

AN:

151400

Hom.:

23204

Cov.:

AF XY:

0.526

AC XY:

38873

AN XY:

73924

show subpopulations

African (AFR)

AF:

0.229

AC:

9437

AN:

41230

American (AMR)

AF:

0.585

AC:

8901

AN:

15214

Ashkenazi Jewish (ASJ)

AF:

0.570

AC:

1973

AN:

3462

East Asian (EAS)

AF:

0.538

AC:

2749

AN:

5106

South Asian (SAS)

AF:

0.582

AC:

2779

AN:

4774

European-Finnish (FIN)

AF:

0.700

AC:

7316

AN:

10446

Middle Eastern (MID)

AF:

0.568

AC:

166

AN:

292

European-Non Finnish (NFE)

AF:

0.649

AC:

44048

AN:

67864

Other (OTH)

AF:

0.555

AC:

1166

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1614

3228

4843

6457

8071

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.609

Hom.:

119648

Bravo

AF:

0.500

Asia WGS

AF:

0.537

AC:

1869

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

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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17-48592068-C-T

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