17-48724867-T-C

Variant names:

• chr17-48724867-T-C
• rs8068566
• NM_006361.6:c.*1923A>G

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.*1923A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HOXB13 NM_006361.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900
• 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]

PRAC2 (HGNC:30143): (PRAC2 small nuclear protein) This gene is highly expressed in prostate, rectum, colon, and testis. This gene may produce a non-coding RNA or may encode a short protein that might localize to the nucleus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

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=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXB13	NM_006361.6	c.*1923A>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000290295.8	NP_006352.2
PRAC2	NM_001282275.2	c.*184T>C		downstream_gene_variant		ENST00000422730.4	NP_001269204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXB13	ENST00000290295.8	c.*1923A>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_006361.6	ENSP00000290295.8
PRAC2	ENST00000422730.4	c.*184T>C		downstream_gene_variant		1	NM_001282275.2	ENSP00000481367.1
PRAC2	ENST00000432056.1	c.*184T>C		downstream_gene_variant		2		ENSP00000484945.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 263618 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 133280

African (AFR) AF: 0.00 AC: 0 AN: 7496

American (AMR) AF: 0.00 AC: 0 AN: 7250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9220

East Asian (EAS) AF: 0.00 AC: 0 AN: 22520

South Asian (SAS) AF: 0.00 AC: 0 AN: 2596

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19982

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 176518

Other (OTH) AF: 0.00 AC: 0 AN: 16726

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.3
DANN	Benign	0.63
PhyloP100		-0.090

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: rs8068566; hg19: chr17-46802229;