17-48530455-C-T

Variant names:

• chr17-48530455-C-T
• rs7207109
• NM_002144.4:c.450G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002144.4(HOXB1):​c.450G>A​(p.Ala150Ala) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.128
• Publications: 29 publications found

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]

HOXB1 Gene-Disease associations (from GenCC):

• facial paresis, hereditary congenital, 3

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• congenital hereditary facial paralysis-variable hearing loss syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000294508 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 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 VariationId is 1281602.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
HOXB1	NM_002144.4	c.450G>A	p.Ala150Ala	synonymous_variant	Exon 1 of 2	ENST00000239174.7	NP_002135.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXB1	ENST00000239174.7	c.450G>A	p.Ala150Ala	synonymous_variant	Exon 1 of 2	1	NM_002144.4	ENSP00000355140.5
HOXB1	ENST00000577092.1	c.450G>A	p.Ala150Ala	synonymous_variant	Exon 1 of 1	6		ENSP00000459066.1
ENSG00000294508	ENST00000724000.1	n.817+2082C>T		intron_variant	Intron 2 of 2

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

GnomAD2 exomes AF: 0.175 AC: 44006 AN: 251286 AF XY: 0.177

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 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

African (AFR) AF: 0.120 AC: 4006 AN: 33478

American (AMR) AF: 0.127 AC: 5686 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 5337 AN: 26132

East Asian (EAS) AF: 0.0575 AC: 2284 AN: 39696

South Asian (SAS) AF: 0.130 AC: 11179 AN: 86252

European-Finnish (FIN) AF: 0.223 AC: 11918 AN: 53412

Middle Eastern (MID) AF: 0.152 AC: 877 AN: 5766

European-Non Finnish (NFE) AF: 0.213 AC: 236668 AN: 1111952

Other (OTH) AF: 0.191 AC: 11537 AN: 60396

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

African (AFR) AF: 0.122 AC: 5044 AN: 41484

American (AMR) AF: 0.155 AC: 2362 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 658 AN: 3470

East Asian (EAS) AF: 0.0867 AC: 449 AN: 5180

South Asian (SAS) AF: 0.137 AC: 659 AN: 4818

European-Finnish (FIN) AF: 0.226 AC: 2390 AN: 10584

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14478 AN: 67938

Other (OTH) AF: 0.191 AC: 403 AN: 2112

Alfa AF: 0.199 Hom.: 5918

Bravo AF: 0.168

Asia WGS AF: 0.138 AC: 479 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.9
DANN	Benign	0.57
PhyloP100		-0.13
PromoterAI		-0.0060	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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