17-48726629-A-AG

Variant names:

• chr17-48726629-A-AG
• rs1597932009
• NM_006361.6:c.*160dupC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006361.6(HOXB13):​c.*160dupC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 717,462 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: HOXB13 NM_006361.6 3_prime_UTR
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.587
• Publications: 0 publications found

Genes affected

HOXB13 (HGNC:5112): (homeobox B13) This gene encodes a transcription factor that belongs to the homeobox gene family. Genes of this family are highly conserved among vertebrates and essential for vertebrate embryonic development. This gene has been implicated to play a role in fetal skin development and cutaneous regeneration. In mice, a similar gene was shown to exhibit temporal and spatial colinearity in the main body axis of the embryo, but was not expressed in the secondary axes, which suggests functions in body patterning along the axis. This gene and other HOXB genes form a gene cluster at chromosome the 17q21-22 region. [provided by RefSeq, Jul 2008]

HOXB13 Gene-Disease associations (from GenCC):

• prostate cancer

  Inheritance: AD Classification: DEFINITIVE Submitted by: Illumina
• prostate cancer, hereditary, 9

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006361.6. 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
	HOXB13	NM_006361.6	MANE Select	c.*160dupC		3_prime_UTR	Exon 2 of 2	NP_006352.2	Q92826

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXB13	ENST00000290295.8	TSL:1 MANE Select	c.*160dupC		3_prime_UTR	Exon 2 of 2	ENSP00000290295.8	Q92826

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 1 AN: 717462 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 362974

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 17336

American (AMR) AF: 0.00 AC: 0 AN: 19114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15288

East Asian (EAS) AF: 0.00 AC: 0 AN: 32222

South Asian (SAS) AF: 0.00 AC: 0 AN: 49982

European-Finnish (FIN) AF: 0.0000281 AC: 1 AN: 35600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2482

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 510852

Other (OTH) AF: 0.00 AC: 0 AN: 34586

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer, hereditary, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.59

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: rs1597932009; hg19: chr17-46803991;