Genetic Variant HOXB7:p.Ser122Asn (chr17-48610554-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_004502.4(HOXB7):c.365G>A(p.Ser122Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000393 in 1,528,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

HOXB7
NM_004502.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.686

Publications

0 publications found

Variant links:

Genes affected

HOXB7 (HGNC:5118): (homeobox B7) 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 nuclear protein functions as a sequence-specific transcription factor that is involved in cell proliferation and differentiation. Increased expression of this gene is associated with some cases of melanoma and ovarian carcinoma. [provided by RefSeq, Jul 2008]

HOXB7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20671222).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004502.4. 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
	HOXB7	NM_004502.4	MANE Select	c.365G>A	p.Ser122Asn	missense	Exon 1 of 2	NP_004493.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXB7	ENST00000239165.9	TSL:1 MANE Select	c.365G>A	p.Ser122Asn	missense	Exon 1 of 2	ENSP00000239165.7	P09629
	HOXB7	ENST00000567101.2	TSL:2	n.60-2459G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000696

AC:

AN:

143628

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000127

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000291

AC:

AN:

1375804

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

675740

show subpopulations

African (AFR)

AF:

0.0000325

AC:

AN:

30734

American (AMR)

AF:

0.0000602

AC:

AN:

33208

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24244

East Asian (EAS)

AF:

0.00

AC:

AN:

34466

South Asian (SAS)

AF:

0.00

AC:

AN:

77790

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47778

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5394

European-Non Finnish (NFE)

AF:

9.39e-7

AC:

AN:

1065396

Other (OTH)

AF:

0.00

AC:

AN:

56794

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

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:

0.0000131

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41446

American (AMR)

AF:

0.000131

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

-0.062

Eigen_PC

Benign

-0.029

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.57

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.21

MetaSVM

Uncertain

-0.048

MutationAssessor

Benign

1.4

PhyloP100

0.69

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.20

REVEL

Benign

0.23

Sift

Benign

0.42

Sift4G

Benign

0.43

Polyphen

0.84

Vest4

0.19

MutPred

0.44

Gain of catalytic residue at S122 (P = 0.0458)

MVP

0.91

MPC

0.52

ClinPred

0.19

GERP RS

2.9

PromoterAI

-0.036

Neutral

(source)

Varity_R

0.17

gMVP

0.44

Mutation Taster

=91/9

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over