rs4646993

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018952.5(HOXB6):​c.-79+238C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 151,852 control chromosomes in the GnomAD database, including 3,364 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 3361 hom., cov: 31)
Exomes 𝑓: 0.18 ( 3 hom. )

Consequence

HOXB6
NM_018952.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.113
Variant links:
Genes affected
HOXB6 (HGNC:5117): (homeobox B6) 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 protein functions as a sequence-specific transcription factor that is involved in development, including that of lung and skin, and has been localized to both the nucleus and cytoplasm. Altered expression of this gene or a change in the subcellular localization of its protein is associated with some cases of acute myeloid leukemia and colorectal cancer. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HOXB6NM_018952.5 linkuse as main transcriptc.-79+238C>G intron_variant ENST00000225648.4 NP_061825.2 P17509-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HOXB6ENST00000225648.4 linkuse as main transcriptc.-79+238C>G intron_variant 1 NM_018952.5 ENSP00000225648.3 P17509-1

Frequencies

GnomAD3 genomes
AF:
0.203
AC:
30696
AN:
151532
Hom.:
3357
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.283
Gnomad AMI
AF:
0.204
Gnomad AMR
AF:
0.173
Gnomad ASJ
AF:
0.181
Gnomad EAS
AF:
0.0617
Gnomad SAS
AF:
0.0990
Gnomad FIN
AF:
0.202
Gnomad MID
AF:
0.190
Gnomad NFE
AF:
0.180
Gnomad OTH
AF:
0.202
GnomAD4 exome
AF:
0.178
AC:
36
AN:
202
Hom.:
3
AF XY:
0.152
AC XY:
20
AN XY:
132
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.218
Gnomad4 NFE exome
AF:
0.121
Gnomad4 OTH exome
AF:
0.167
GnomAD4 genome
AF:
0.203
AC:
30720
AN:
151650
Hom.:
3361
Cov.:
31
AF XY:
0.201
AC XY:
14890
AN XY:
74090
show subpopulations
Gnomad4 AFR
AF:
0.283
Gnomad4 AMR
AF:
0.173
Gnomad4 ASJ
AF:
0.181
Gnomad4 EAS
AF:
0.0613
Gnomad4 SAS
AF:
0.0997
Gnomad4 FIN
AF:
0.202
Gnomad4 NFE
AF:
0.180
Gnomad4 OTH
AF:
0.198
Alfa
AF:
0.196
Hom.:
383
Bravo
AF:
0.205
Asia WGS
AF:
0.105
AC:
367
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
3.8
DANN
Benign
0.59
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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.

Other links and lift over

dbSNP: rs4646993; hg19: chr17-46681604; API