rs7207109

chr17-48530455-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_002144.4(HOXB1):c.450G>A(p.Ala150=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,613,872 control chromosomes in the GnomAD database, including 32,419 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (2557 hom., cov: 32)
  • Exomes 𝑓: 0.20 (29862 hom.)
• Consequence: HOXB1 NM_002144.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.128

Genes affected

HOXB1 (HGNC:5111): (homeobox B1) This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, located on different chromosomes, consisting of 9 to 11 genes arranged in tandem. This gene is one of several homeobox HOXB genes located in a cluster on chromosome 17. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 17-48530455-C-T is Benign according to our data. Variant chr17-48530455-C-T is described in ClinVar as [Benign]. Clinvar id is 1281602.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-48530455-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.128 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOXB1	NM_002144.4	c.450G>A	p.Ala150=	synonymous_variant	1/2	ENST00000239174.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOXB1	ENST00000239174.7	c.450G>A	p.Ala150=	synonymous_variant	1/2	1	NM_002144.4	P1
HOXB1	ENST00000577092.1	c.450G>A	p.Ala150=	synonymous_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26779 AN: 151960 Hom.: 2557 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.0871

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.194

GnomAD3 exomes AF: 0.175 AC: 44006 AN: 251286 Hom.: 4226 AF XY: 0.177 AC XY: 23980 AN XY: 135806

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.123

Gnomad ASJ exome AF: 0.201

Gnomad EAS exome AF: 0.0889

Gnomad SAS exome AF: 0.128

Gnomad FIN exome AF: 0.224

Gnomad NFE exome AF: 0.213

Gnomad OTH exome AF: 0.192

GnomAD4 exome AF: 0.198 AC: 289492 AN: 1461794 Hom.: 29862 Cov.: 34 AF XY: 0.196 AC XY: 142803 AN XY: 727196

Gnomad4 AFR exome AF: 0.120

Gnomad4 AMR exome AF: 0.127

Gnomad4 ASJ exome AF: 0.204

Gnomad4 EAS exome AF: 0.0575

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.223

Gnomad4 NFE exome AF: 0.213

Gnomad4 OTH exome AF: 0.191

GnomAD4 genome AF: 0.176 AC: 26788 AN: 152078 Hom.: 2557 Cov.: 32 AF XY: 0.175 AC XY: 13029 AN XY: 74344

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.0867

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.191

Alfa AF: 0.202 Hom.: 4524

Bravo AF: 0.168

Asia WGS AF: 0.138 AC: 479 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	1.9
Dann	Benign	0.57

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: rs7207109; hg19: chr17-46607817; COSMIC: COSV53318223;