chr17-48592068-C-T

Position:

• chr17-48592068-C-T

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXB5	NM_002147.4	c.*141G>A		3_prime_UTR_variant	2/2	ENST00000239151.6	NP_002138.1
HOXB-AS3	NR_033201.2	n.170+1479C>T		intron_variant
HOXB-AS3	NR_033202.2	n.170+1479C>T		intron_variant
HOXB-AS3	NR_110331.1	n.170+1479C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXB5	ENST00000239151.6	c.*141G>A		3_prime_UTR_variant	2/2	1	NM_002147.4	ENSP00000239151.4

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

Gnomad4 AFR exome AF: 0.219

Gnomad4 AMR exome AF: 0.594

Gnomad4 ASJ exome AF: 0.565

Gnomad4 EAS exome AF: 0.565

Gnomad4 SAS exome AF: 0.598

Gnomad4 FIN exome AF: 0.690

Gnomad4 NFE exome AF: 0.649

Gnomad4 OTH exome AF: 0.598

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

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.585

Gnomad4 ASJ AF: 0.570

Gnomad4 EAS AF: 0.538

Gnomad4 SAS AF: 0.582

Gnomad4 FIN AF: 0.700

Gnomad4 NFE AF: 0.649

Gnomad4 OTH AF: 0.555

Alfa AF: 0.627 Hom.: 58839

Bravo AF: 0.500

Asia WGS AF: 0.537 AC: 1869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	18
DANN	Benign	0.95

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: rs9299; hg19: chr17-46669430; COSMIC: COSV53312049; COSMIC: COSV53312049;