rs4646993

Positions:

• chr17-48604242-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113

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]

HOXB-AS3 (HGNC:):

ACMG classification

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
HOXB6	NM_018952.5	c.-79+238C>G		intron_variant		ENST00000225648.4	NP_061825.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXB6	ENST00000225648.4	c.-79+238C>G		intron_variant		1	NM_018952.5	ENSP00000225648.3

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30696 AN: 151532 Hom.: 3357 Cov.: 31

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

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

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

Other links and lift over

dbSNP: rs4646993; hg19: chr17-46681604;