17-48530421-C-T

Variant names:

• chr17-48530421-C-T
• rs144625073
• NM_002144.4:c.484G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_002144.4(HOXB1):​c.484G>A​(p.Glu162Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000793 in 1,614,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: HOXB1 NM_002144.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 2.62

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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011893094).
• BP6: Variant 17-48530421-C-T is Benign according to our data. Variant chr17-48530421-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 800233.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXB1	NM_002144.4	c.484G>A	p.Glu162Lys	missense_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.484G>A	p.Glu162Lys	missense_variant	Exon 1 of 2	1	NM_002144.4	ENSP00000355140.5
HOXB1	ENST00000577092.1	c.484G>A	p.Glu162Lys	missense_variant	Exon 1 of 1	6		ENSP00000459066.1

Frequencies

GnomAD3 genomes AF: 0.000454 AC: 69 AN: 152106 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00162

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000119 AC: 30 AN: 251382 AF XY: 0.0000957

Gnomad AFR exome AF: 0.00185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000397 AC: 58 AN: 1461866 Hom.: 0 Cov.: 31 AF XY: 0.0000426 AC XY: 31 AN XY: 727230

Gnomad4 AFR exome AF: 0.00149 AC: 50 AN: 33480

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 44718

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26136

Gnomad4 EAS exome AF: 0.0000252 AC: 1 AN: 39700

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 86258

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53418

Gnomad4 NFE exome AF: 0.00000270 AC: 3 AN: 1111992

Gnomad4 Remaining exome AF: 0.0000662 AC: 4 AN: 60396

GnomAD4 genome AF: 0.000460 AC: 70 AN: 152224 Hom.: 0 Cov.: 32 AF XY: 0.000484 AC XY: 36 AN XY: 74420

Gnomad4 AFR AF: 0.00164 AC: 0.00163761 AN: 0.00163761

Gnomad4 AMR AF: 0.0000653 AC: 0.0000653253 AN: 0.0000653253

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000207 AC: 0.000207125 AN: 0.000207125

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.00 AC: 0 AN: 0

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

Alfa AF: 0.0000944 Hom.: 0

Bravo AF: 0.000476

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000189 AC: 23

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 13, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

HOXB1-related disorder Benign:1

Feb 18, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;T;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.85	.;T;D
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.012	T;T;T
MetaSVM	Benign	-0.32	T
MutationAssessor	Uncertain	2.6	M;M;M
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.88	N;.;.
REVEL	Uncertain	0.44
Sift	Benign	0.38	T;.;.
Sift4G	Benign	0.65	T;.;T
Polyphen		0.70	P;P;.
Vest4		0.48
MVP		0.89
MPC		0.86
ClinPred		0.13	T
GERP RS		3.5
Varity_R		0.18
gMVP		0.56
Mutation Taster		=86/14	polymorphism

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: rs144625073; hg19: chr17-46607783;