dbSNP rs4646993: HOXB6:c.-79+238C>G (chr17-48604242-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_018952.5(HOXB6):c.-79+238C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 151,852 control chromosomes in the GnomAD database, including 3,364 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 0.20 ( 3361 hom., cov: 31)

Exomes 𝑓: 0.18 ( 3 hom. )

Consequence

HOXB6
NM_018952.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.113

Publications

6 publications found

Variant links:

Genes affected

HOXB6 (HGNC:5117): (homeobox B6) This gene is a member of the Antp homeobox family and encodes a 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, including that of lung and skin, and has been localized to both the nucleus and cytoplasm. Altered expression of this gene or a change in the subcellular localization of its protein is associated with some cases of acute myeloid leukemia and colorectal cancer. [provided by RefSeq, Jul 2008]

HOXB6 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXB6	NM_018952.5 link	c.-79+238C>G		intron_variant	Intron 2 of 3	ENST00000225648.4	NP_061825.2	P17509-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXB6	ENST00000225648.4 link	c.-79+238C>G		intron_variant	Intron 2 of 3	1	NM_018952.5	ENSP00000225648.3		P17509-1

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30696

AN:

151532

Hom.:

3357

Cov.:

show subpopulations

Gnomad AFR

AF:

0.283

Gnomad AMI

AF:

0.204

Gnomad AMR

AF:

0.173

Gnomad ASJ

AF:

0.181

Gnomad EAS

AF:

0.0617

Gnomad SAS

AF:

0.0990

Gnomad FIN

AF:

0.202

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.180

Gnomad OTH

AF:

0.202

GnomAD4 exome

AF:

0.178

AC:

AN:

202

Hom.:

AF XY:

0.152

AC XY:

AN XY:

132

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.218

AC:

AN:

124

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.121

AC:

AN:

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.203

AC:

30720

AN:

151650

Hom.:

3361

Cov.:

AF XY:

0.201

AC XY:

14890

AN XY:

74090

show subpopulations

African (AFR)

AF:

0.283

AC:

11679

AN:

41282

American (AMR)

AF:

0.173

AC:

2639

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.181

AC:

626

AN:

3466

East Asian (EAS)

AF:

0.0613

AC:

316

AN:

5158

South Asian (SAS)

AF:

0.0997

AC:

479

AN:

4804

European-Finnish (FIN)

AF:

0.202

AC:

2129

AN:

10534

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.180

AC:

12198

AN:

67868

Other (OTH)

AF:

0.198

AC:

415

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

1140

2281

3421

4562

5702

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

322

644

966

1288

1610

<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:

0.196

Hom.:

383

Bravo

AF:

0.205

Asia WGS

AF:

0.105

AC:

367

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.8

(source)

DANN

Benign

0.59

PhyloP100

-0.11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over