chr17-48726650-C-T

Variant names:

• chr17-48726650-C-T
• rs1597932075
• NM_006361.6:c.*140G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006361.6(HOXB13):​c.*140G>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 0.00000107 in 938,792 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: HOXB13 NM_006361.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.309
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).

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.*140G>A		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.*140G>A		3_prime_UTR	Exon 2 of 2	ENSP00000290295.8	Q92826

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000107 AC: 1 AN: 938792 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 468040

African (AFR) AF: 0.00 AC: 0 AN: 21598

American (AMR) AF: 0.00 AC: 0 AN: 21050

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16960

East Asian (EAS) AF: 0.00 AC: 0 AN: 33590

South Asian (SAS) AF: 0.00 AC: 0 AN: 56384

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2928

European-Non Finnish (NFE) AF: 0.00000142 AC: 1 AN: 704554

Other (OTH) AF: 0.00 AC: 0 AN: 41650

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	9.8
DANN	Benign	0.77
PhyloP100		0.31

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: rs1597932075; hg19: chr17-46804012;