Variant chr17-48613497-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024016.4(HOXB8):c.437G>C(p.Arg146Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000171 in 1,170,772 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 28)

Exomes 𝑓: 0.0000017 ( 0 hom. )

Consequence

HOXB8
NM_024016.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.93

Variant links:

Genes affected

HOXB8 (HGNC:5119): (homeobox B8) This gene is a member of the Antp homeobox family and encodes a nuclear protein with a homeobox DNA-binding domain. It is included in a cluster of homeobox B genes located on chromosome 17. The encoded protein functions as a sequence-specific transcription factor that is involved in development. Increased expression of this gene is associated with colorectal cancer. Mice that have had the murine ortholog of this gene knocked out exhibit an excessive pathologic grooming behavior. This behavior is similar to the behavior of humans suffering from the obsessive-compulsive spectrum disorder trichotillomania. [provided by RefSeq, Jul 2008]

HOXB8 links:

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOXB8	NM_024016.4 linkuse as main transcript	c.437G>C	p.Arg146Pro	missense_variant	2/2	ENST00000239144.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
HOXB8	ENST00000239144.5 linkuse as main transcript	c.437G>C	p.Arg146Pro	missense_variant	2/2	2	NM_024016.4	P4
HOXB8	ENST00000576562.1 linkuse as main transcript	c.434G>C	p.Arg145Pro	missense_variant	2/2	2		A1
HOXB7	ENST00000567101.2 linkuse as main transcript	n.60-5402G>C		intron_variant, non_coding_transcript_variant		2
HOXB8	ENST00000498634.2 linkuse as main transcript			upstream_gene_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000419

AC:

AN:

238908

Hom.:

AF XY:

0.00

AC XY:

AN XY:

129776

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00000918

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000171

AC:

AN:

1170772

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

577364

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000217

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 09, 2023

The c.437G>C (p.R146P) alteration is located in exon 2 (coding exon 2) of the HOXB8 gene. This alteration results from a G to C substitution at nucleotide position 437, causing the arginine (R) at amino acid position 146 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.48

T;T

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.85

D;D

M_CAP

Pathogenic

0.56

MetaRNN

Uncertain

0.48

T;T

MetaSVM

Pathogenic

0.97

MutationAssessor

Uncertain

2.5

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.91

PROVEAN

Pathogenic

-5.5

D;.

REVEL

Pathogenic

0.74

Sift

Uncertain

0.0050

D;.

Sift4G

Uncertain

0.0030

D;D

Polyphen

1.0

D;.

Vest4

0.40

MutPred

0.40

Loss of methylation at R146 (P = 0.0312);.;

MVP

0.96

MPC

2.5

ClinPred

0.98

GERP RS

3.1

Varity_R

0.84

gMVP

0.78

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