17-48542733-G-T

Position:

• chr17-48542733-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002145.4(HOXB2):​c.*335C>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 0.158 in 190,770 control chromosomes in the GnomAD database, including 2,678 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 0.16 (2080 hom., cov: 32)
  • Exomes 𝑓: 0.16 (598 hom.)
• Consequence: HOXB2 NM_002145.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.00

Genes affected

HOXB2 (HGNC:5113): (homeobox B2) 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 pancreatic cancer. [provided by RefSeq, Jul 2008]

HOXB2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXB2	NM_002145.4	c.*335C>A		3_prime_UTR_variant	2/2	ENST00000330070.6	NP_002136.1
HOXB2	XM_005257275.5	c.*335C>A		3_prime_UTR_variant	2/2		XP_005257332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXB2	ENST00000330070	c.*335C>A		3_prime_UTR_variant	2/2	1	NM_002145.4	ENSP00000331741.4
HOXB2	ENST00000504772.3	n.192+222C>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23785 AN: 152046 Hom.: 2079 Cov.: 32

Gnomad AFR AF: 0.0812

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.0859

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.168

GnomAD4 exome AF: 0.163 AC: 6285 AN: 38606 Hom.: 598 Cov.: 0 AF XY: 0.163 AC XY: 3221 AN XY: 19728

Gnomad4 AFR exome AF: 0.0717

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.170

Gnomad4 EAS exome AF: 0.0392

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.205

Gnomad4 NFE exome AF: 0.182

Gnomad4 OTH exome AF: 0.146

GnomAD4 genome AF: 0.156 AC: 23790 AN: 152164 Hom.: 2080 Cov.: 32 AF XY: 0.157 AC XY: 11681 AN XY: 74396

Gnomad4 AFR AF: 0.0813

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.0855

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.165

Alfa AF: 0.177 Hom.: 471

Bravo AF: 0.148

Asia WGS AF: 0.131 AC: 454 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	17
DANN	Benign	0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0

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: rs1042822; hg19: chr17-46620095;