chr17-48604242-G-C

Variant names:

• chr17-48604242-G-C
• rs4646993
• NM_018952.5:c.-79+238C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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:40283): (HOXB cluster antisense RNA 3)

HOXB3 (HGNC:5114): (homeobox B3) 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 a distinct biologic subset of acute myeloid leukemia (AML). [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018952.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXB6	NM_018952.5	MANE Select	c.-79+238C>G		intron	N/A	NP_061825.2
	HOXB6	NM_001369397.2		c.-111+238C>G		intron	N/A	NP_001356326.1
	HOXB-AS3	NR_033201.2		n.290+196G>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXB6	ENST00000225648.4	TSL:1 MANE Select	c.-79+238C>G		intron	N/A	ENSP00000225648.3
	HOXB6	ENST00000484302.3	TSL:2	c.-111+238C>G		intron	N/A	ENSP00000420009.2
	HOXB-AS3	ENST00000466037.6	TSL:3	n.259+196G>C		intron	N/A

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

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.218 AC: 27 AN: 124

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.121 AC: 7 AN: 58

Other (OTH) AF: 0.167 AC: 2 AN: 12

GnomAD4 genome AF: 0.203 AC: 30720 AN: 151650 Hom.: 3361 Cov.: 31 AF XY: 0.201 AC XY: 14890 AN XY: 74090

African (AFR) AF: 0.283 AC: 11679 AN: 41282

American (AMR) AF: 0.173 AC: 2639 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 626 AN: 3466

East Asian (EAS) AF: 0.0613 AC: 316 AN: 5158

South Asian (SAS) AF: 0.0997 AC: 479 AN: 4804

European-Finnish (FIN) AF: 0.202 AC: 2129 AN: 10534

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12198 AN: 67868

Other (OTH) AF: 0.198 AC: 415 AN: 2094

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.8
DANN	Benign	0.59
PhyloP100		-0.11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4646993; hg19: chr17-46681604;