17-48728264-G-T

Position:

• chr17-48728264-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_006361.6(HOXB13):​c.330C>A​(p.Pro110Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00154 in 1,614,186 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0064 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (13 hom.)
• Consequence: HOXB13 NM_006361.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.0580

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 17-48728264-G-T is Benign according to our data. Variant chr17-48728264-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 480872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-48728264-G-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.058 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0064 (975/152334) while in subpopulation AFR AF= 0.0209 (870/41582). AF 95% confidence interval is 0.0198. There are 10 homozygotes in gnomad4. There are 481 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXB13	NM_006361.6	c.330C>A	p.Pro110Pro	synonymous_variant	1/2	ENST00000290295.8	NP_006352.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXB13	ENST00000290295.8	c.330C>A	p.Pro110Pro	synonymous_variant	1/2	1	NM_006361.6	ENSP00000290295.8

Frequencies

GnomAD3 genomes AF: 0.00635 AC: 966 AN: 152216 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0208

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00307

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00240 AC: 602 AN: 251064 Hom.: 2 AF XY: 0.00200 AC XY: 272 AN XY: 135824

Gnomad AFR exome AF: 0.0212

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.0156

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.000387

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00103 AC: 1511 AN: 1461852 Hom.: 13 Cov.: 33 AF XY: 0.00103 AC XY: 750 AN XY: 727224

Gnomad4 AFR exome AF: 0.0209

Gnomad4 AMR exome AF: 0.00157

Gnomad4 ASJ exome AF: 0.0143

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000172

Gnomad4 OTH exome AF: 0.00232

GnomAD4 genome AF: 0.00640 AC: 975 AN: 152334 Hom.: 10 Cov.: 32 AF XY: 0.00646 AC XY: 481 AN XY: 74492

Gnomad4 AFR AF: 0.0209

Gnomad4 AMR AF: 0.00307

Gnomad4 ASJ AF: 0.0118

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00503 Hom.: 2

Bravo AF: 0.00769

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000356

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Sep 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Quest Diagnostics Nichols Institute San Juan Capistrano	Jul 20, 2021	- -

Prostate cancer, hereditary, 9 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Hereditary cancer-predisposing syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2018

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	4.7
DANN	Benign	0.90

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: rs33993186; hg19: chr17-46805626;