rs12939811

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 1239766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-48530596-T-A is described in Lovd as [Benign].

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
HOXB1	NM_002144.4 link	c.309A>T	p.Gln103His	missense_variant	Exon 1 of 2	ENST00000239174.7	NP_002135.2	P14653-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXB1	ENST00000239174.7 link	c.309A>T	p.Gln103His	missense_variant	Exon 1 of 2	1	NM_002144.4	ENSP00000355140.5		P14653-1
HOXB1	ENST00000577092.1 link	c.309A>T	p.Gln103His	missense_variant	Exon 1 of 1	6		ENSP00000459066.1		P14653-2

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

GnomAD3 exomes

AF:

0.161

AC:

40355

AN:

250544

Hom.:

3617

AF XY:

0.163

AC XY:

22128

AN XY:

135592

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 SAS exome

AF:

0.123

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

Gnomad4 AFR exome

AF:

0.0718

Gnomad4 AMR exome

AF:

0.113

Gnomad4 ASJ exome

AF:

0.194

Gnomad4 EAS exome

AF:

0.0575

Gnomad4 SAS exome

AF:

0.124

Gnomad4 FIN exome

AF:

0.221

Gnomad4 NFE exome

AF:

0.196

Gnomad4 OTH exome

AF:

0.174

GnomAD4 genome

AF:

0.153

AC:

23258

AN:

152194

Hom.:

2043

Cov.:

AF XY:

0.153

AC XY:

11384

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0749

Gnomad4 AMR

AF:

0.135

Gnomad4 ASJ

AF:

0.183

Gnomad4 EAS

AF:

0.0878

Gnomad4 SAS

AF:

0.132

Gnomad4 FIN

AF:

0.223

Gnomad4 NFE

AF:

0.196

Gnomad4 OTH

AF:

0.163

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.41

CADD

Benign

5.4

DANN

Benign

0.83

DEOGEN2

Benign

0.22

T;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.45

.;T;T

MetaRNN

Benign

0.0012

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.8

L;L;L

PrimateAI

Benign

0.45

PROVEAN

Benign

-2.3

N;.;.

REVEL

Uncertain

0.36

Sift

Uncertain

0.015

D;.;.

Sift4G

Benign

0.077

T;.;D

Polyphen

0.64

P;P;.

Vest4

0.26

MutPred

0.10

Gain of catalytic residue at Q103 (P = 0.0787);Gain of catalytic residue at Q103 (P = 0.0787);Gain of catalytic residue at Q103 (P = 0.0787);

MPC

0.71

ClinPred

0.030

GERP RS

-5.7

Varity_R

0.13

gMVP

0.48

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over