dbSNP rs144625073: HOXB1:p.Glu162Gln (chr17-48530421-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002144.4(HOXB1):c.484G>C(p.Glu162Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,613,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

HOXB1
NM_002144.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.62

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08045408).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXB1	NM_002144.4 link	c.484G>C	p.Glu162Gln	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.484G>C	p.Glu162Gln	missense_variant	Exon 1 of 2	1	NM_002144.4	ENSP00000355140.5		P14653-1
HOXB1	ENST00000577092.1 link	c.484G>C	p.Glu162Gln	missense_variant	Exon 1 of 1	6		ENSP00000459066.1		P14653-2

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251382

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1461866

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.000362

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000217

Hom.:

Bravo

AF:

0.000106

ExAC

AF:

0.0000494

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.070

T;T;.

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.73

.;T;T

M_CAP

Benign

0.059

MetaRNN

Benign

0.080

T;T;T

MetaSVM

Uncertain

-0.029

MutationAssessor

Benign

1.2

L;L;L

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.030

N;.;.

REVEL

Benign

0.20

Sift

Benign

0.41

T;.;.

Sift4G

Benign

0.47

T;.;T

Polyphen

0.98

D;D;.

Vest4

0.14

MutPred

0.24

Loss of solvent accessibility (P = 0.0721);Loss of solvent accessibility (P = 0.0721);Loss of solvent accessibility (P = 0.0721);

MVP

0.93

MPC

1.1

ClinPred

0.11

GERP RS

3.5

Varity_R

0.14

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over