17-48529659-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002144.4(HOXB1):c.794A>G(p.Glu265Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.997 in 1,610,438 control chromosomes in the GnomAD database, including 801,135 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.99 ( 74118 hom., cov: 32)

Exomes 𝑓: 1.0 ( 727017 hom. )

Consequence

HOXB1
NM_002144.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.09

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.513341E-7).

BP6

Variant 17-48529659-T-C is Benign according to our data. Variant chr17-48529659-T-C is described in ClinVar as [Benign]. Clinvar id is 1175019.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-48529659-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXB1	NM_002144.4 link	c.794A>G	p.Glu265Gly	missense_variant	Exon 2 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.794A>G	p.Glu265Gly	missense_variant	Exon 2 of 2	1	NM_002144.4	ENSP00000355140.5		P14653-1
HOXB1	ENST00000577092 link	c.*547A>G		3_prime_UTR_variant	Exon 1 of 1			ENSP00000459066.1		P14653-2

Frequencies

GnomAD3 genomes

AF:

0.986

AC:

150115

AN:

152200

Hom.:

74065

Cov.:

show subpopulations

Gnomad AFR

AF:

0.952

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.996

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.988

GnomAD3 exomes

AF:

0.996

AC:

250022

AN:

250964

Hom.:

124561

AF XY:

0.997

AC XY:

135272

AN XY:

135638

show subpopulations

Gnomad AFR exome

AF:

0.949

Gnomad AMR exome

AF:

0.998

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.998

GnomAD4 exome

AF:

0.999

AC:

1456033

AN:

1458120

Hom.:

727017

Cov.:

AF XY:

0.999

AC XY:

723670

AN XY:

724584

show subpopulations

Gnomad4 AFR exome

AF:

0.950

Gnomad4 AMR exome

AF:

0.997

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.997

GnomAD4 genome

AF:

0.986

AC:

150227

AN:

152318

Hom.:

74118

Cov.:

AF XY:

0.987

AC XY:

73494

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.952

Gnomad4 AMR

AF:

0.996

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.988

Alfa

AF:

0.997

Hom.:

116136

Bravo

AF:

0.984

TwinsUK

AF:

1.00

AC:

3708

ALSPAC

AF:

1.00

AC:

3854

ESP6500AA

AF:

0.953

AC:

4198

ESP6500EA

AF:

1.00

AC:

8600

ExAC

AF:

0.996

AC:

120862

Asia WGS

AF:

0.998

AC:

3472

AN:

3478

EpiCase

AF:

1.00

EpiControl

AF:

1.00

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

- -

Facial paresis, hereditary congenital, 3

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.043

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.070

T;T

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.029

.;T

MetaRNN

Benign

5.5e-7

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-2.0

N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

4.5

N;.

REVEL

Uncertain

0.30

Sift

Benign

0.74

T;.

Sift4G

Benign

1.0

T;.

Polyphen

0.0

B;B

Vest4

0.029

MPC

0.50

ClinPred

0.0048

GERP RS

5.2

Varity_R

0.049

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