17-48530596-T-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002144.4(HOXB1):c.309A>T(p.Gln103His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 1,613,906 control chromosomes in the GnomAD database, including 27,379 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. Q103Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.15 ( 2043 hom., cov: 32)

Exomes 𝑓: 0.18 ( 25336 hom. )

Consequence

HOXB1
NM_002144.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.43

Publications

37 publications found

Variant links:

Genes affected

HOXB1 (HGNC:5111): (homeobox B1) This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, located on different chromosomes, consisting of 9 to 11 genes arranged in tandem. This gene is one of several homeobox HOXB genes located in a cluster on chromosome 17. [provided by RefSeq, Jul 2008]

HOXB1 Gene-Disease associations (from GenCC):

facial paresis, hereditary congenital, 3
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
congenital hereditary facial paralysis-variable hearing loss syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

HOXB1 links:

ENSG00000294508 (HGNC:):

ENSG00000294508 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011953115).

BP6

Variant 17-48530596-T-A is Benign according to our data. Variant chr17-48530596-T-A is described in ClinVar as Benign. ClinVar VariationId is 1239766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002144.4. 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
	HOXB1	NM_002144.4	MANE Select	c.309A>T	p.Gln103His	missense	Exon 1 of 2	NP_002135.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HOXB1	ENST00000239174.7	TSL:1 MANE Select	c.309A>T	p.Gln103His	missense	Exon 1 of 2	ENSP00000355140.5	P14653-1
HOXB1	ENST00000577092.1	TSL:6	c.309A>T	p.Gln103His	missense	Exon 1 of 1	ENSP00000459066.1	P14653-2
ENSG00000294508	ENST00000724000.1		n.817+2223T>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

23256

AN:

152076

Hom.:

2042

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0749

Gnomad AMI

AF:

0.295

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.183

Gnomad EAS

AF:

0.0881

Gnomad SAS

AF:

0.132

Gnomad FIN

AF:

0.223

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.196

Gnomad OTH

AF:

0.166

GnomAD2 exomes

AF:

0.161

AC:

40355

AN:

250544

AF XY:

0.163

show subpopulations

Gnomad AFR exome

AF:

0.0733

Gnomad AMR exome

AF:

0.110

Gnomad ASJ exome

AF:

0.190

Gnomad EAS exome

AF:

0.0889

Gnomad FIN exome

AF:

0.222

Gnomad NFE exome

AF:

0.196

Gnomad OTH exome

AF:

0.178

GnomAD4 exome

AF:

0.182

AC:

266168

AN:

1461712

Hom.:

25336

Cov.:

AF XY:

0.181

AC XY:

131342

AN XY:

727164

show subpopulations

African (AFR)

AF:

0.0718

AC:

2403

AN:

33478

American (AMR)

AF:

0.113

AC:

5048

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.194

AC:

5057

AN:

26134

East Asian (EAS)

AF:

0.0575

AC:

2284

AN:

39700

South Asian (SAS)

AF:

0.124

AC:

10706

AN:

86256

European-Finnish (FIN)

AF:

0.221

AC:

11796

AN:

53306

Middle Eastern (MID)

AF:

0.142

AC:

818

AN:

5768

European-Non Finnish (NFE)

AF:

0.196

AC:

217531

AN:

1111962

Other (OTH)

AF:

0.174

AC:

10525

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

13752

27504

41255

55007

68759

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7468

14936

22404

29872

37340

<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:

0.153

AC:

23258

AN:

152194

Hom.:

2043

Cov.:

AF XY:

0.153

AC XY:

11384

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.0749

AC:

3114

AN:

41560

American (AMR)

AF:

0.135

AC:

2068

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.183

AC:

634

AN:

3472

East Asian (EAS)

AF:

0.0878

AC:

452

AN:

5150

South Asian (SAS)

AF:

0.132

AC:

640

AN:

4832

European-Finnish (FIN)

AF:

0.223

AC:

2367

AN:

10602

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.196

AC:

13320

AN:

67972

Other (OTH)

AF:

0.163

AC:

343

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1041

2083

3124

4166

5207

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

252

504

756

1008

1260

<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:

0.171

Hom.:

1858

Bravo

AF:

0.142

TwinsUK

AF:

0.203

AC:

751

ALSPAC

AF:

0.187

AC:

721

ESP6500AA

AF:

0.0778

AC:

343

ESP6500EA

AF:

0.188

AC:

1621

ExAC

AF:

0.161

AC:

19528

Asia WGS

AF:

0.131

AC:

455

AN:

3478

EpiCase

AF:

0.195

EpiControl

AF:

0.194

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.41

CADD

Benign

5.4

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.22

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.45

MetaRNN

Benign

0.0012

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.8

PhyloP100

-1.4

PrimateAI

Benign

0.45

PROVEAN

Benign

-2.3

REVEL

Uncertain

0.36

Sift

Uncertain

0.015

Sift4G

Benign

0.077

Polyphen

0.64

Vest4

0.26

MutPred

0.10

Gain of catalytic residue at Q103 (P = 0.0787)

MPC

0.71

ClinPred

0.030

GERP RS

-5.7

PromoterAI

-0.0078

Neutral

(source)

Varity_R

0.13

gMVP

0.48

Mutation Taster

=99/1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over