rs1042815

Positions:

• chr17-48542926-G-A
• chr17-48542926-G-C

Variant summary

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

The NM_002145.4(HOXB2):​c.*142C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 510,568 control chromosomes in the GnomAD database, including 91,279 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 (22840 hom., cov: 31)
  • Exomes 𝑓: 0.61 (68439 hom.)
• Consequence: HOXB2 NM_002145.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOXB2	NM_002145.4	c.*142C>T		3_prime_UTR_variant	2/2	ENST00000330070.6
HOXB2	XM_005257275.5	c.*142C>T		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOXB2	ENST00000330070.6	c.*142C>T		3_prime_UTR_variant	2/2	1	NM_002145.4	P1
HOXB2	ENST00000504772.3	n.192+29C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79604 AN: 151868 Hom.: 22819 Cov.: 31

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.568

GnomAD4 exome AF: 0.611 AC: 218996 AN: 358580 Hom.: 68439 Cov.: 5 AF XY: 0.614 AC XY: 112312 AN XY: 183052

Gnomad4 AFR exome AF: 0.256

Gnomad4 AMR exome AF: 0.692

Gnomad4 ASJ exome AF: 0.632

Gnomad4 EAS exome AF: 0.722

Gnomad4 SAS exome AF: 0.702

Gnomad4 FIN exome AF: 0.588

Gnomad4 NFE exome AF: 0.607

Gnomad4 OTH exome AF: 0.594

GnomAD4 genome AF: 0.524 AC: 79651 AN: 151988 Hom.: 22840 Cov.: 31 AF XY: 0.529 AC XY: 39312 AN XY: 74288

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.661

Gnomad4 ASJ AF: 0.641

Gnomad4 EAS AF: 0.668

Gnomad4 SAS AF: 0.701

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.611

Gnomad4 OTH AF: 0.571

Alfa AF: 0.594 Hom.: 38205

Bravo AF: 0.516

Asia WGS AF: 0.665 AC: 2315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.79

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: rs1042815; hg19: chr17-46620288; COSMIC: COSV57486188; COSMIC: COSV57486188;