17-48592068-C-T

Variant names:

• chr17-48592068-C-T
• rs9299
• NM_002147.4:c.*141G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002147.4(HOXB5):​c.*141G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 884,580 control chromosomes in the GnomAD database, including 169,944 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 0.52 (23204 hom., cov: 28)
  • Exomes 𝑓: 0.63 (146740 hom.)
• Consequence: HOXB5 NM_002147.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.03
• Publications: 85 publications found

Genes affected

HOXB5 (HGNC:5116): (homeobox B5) 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 lung and gut development. Increased expression of this gene is associated with a distinct biologic subset of acute myeloid leukemia (AML) and the occurrence of bronchopulmonary sequestration (BPS) and congenital cystic adenomatoid malformation (CCAM) tissue. [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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002147.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXB5	NM_002147.4	MANE Select	c.*141G>A		3_prime_UTR	Exon 2 of 2	NP_002138.1	P09067
	HOXB-AS3	NR_033201.2		n.170+1479C>T		intron	N/A
	HOXB-AS3	NR_033202.2		n.170+1479C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXB5	ENST00000239151.6	TSL:1 MANE Select	c.*141G>A		3_prime_UTR	Exon 2 of 2	ENSP00000239151.4	P09067
	HOXB-AS3	ENST00000465846.6	TSL:3	n.78-8379C>T		intron	N/A
	HOXB-AS3	ENST00000467155.7	TSL:2	n.193+1479C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79038 AN: 151284 Hom.: 23199 Cov.: 28

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.552

GnomAD4 exome AF: 0.627 AC: 459452 AN: 733180 Hom.: 146740 Cov.: 10 AF XY: 0.628 AC XY: 234515 AN XY: 373676

African (AFR) AF: 0.219 AC: 4012 AN: 18290

American (AMR) AF: 0.594 AC: 12344 AN: 20776

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 8785 AN: 15550

East Asian (EAS) AF: 0.565 AC: 18765 AN: 33218

South Asian (SAS) AF: 0.598 AC: 32206 AN: 53816

European-Finnish (FIN) AF: 0.690 AC: 22022 AN: 31900

Middle Eastern (MID) AF: 0.610 AC: 1515 AN: 2482

European-Non Finnish (NFE) AF: 0.649 AC: 338534 AN: 521586

Other (OTH) AF: 0.598 AC: 21269 AN: 35562

GnomAD4 genome AF: 0.522 AC: 79059 AN: 151400 Hom.: 23204 Cov.: 28 AF XY: 0.526 AC XY: 38873 AN XY: 73924

African (AFR) AF: 0.229 AC: 9437 AN: 41230

American (AMR) AF: 0.585 AC: 8901 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1973 AN: 3462

East Asian (EAS) AF: 0.538 AC: 2749 AN: 5106

South Asian (SAS) AF: 0.582 AC: 2779 AN: 4774

European-Finnish (FIN) AF: 0.700 AC: 7316 AN: 10446

Middle Eastern (MID) AF: 0.568 AC: 166 AN: 292

European-Non Finnish (NFE) AF: 0.649 AC: 44048 AN: 67864

Other (OTH) AF: 0.555 AC: 1166 AN: 2102

Alfa AF: 0.609 Hom.: 119648

Bravo AF: 0.500

Asia WGS AF: 0.537 AC: 1869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	18
DANN	Benign	0.95
PhyloP100		2.0
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: rs9299; hg19: chr17-46669430; COSMIC: COSV53312049; COSMIC: COSV53312049;