chr17-48614540-C-G

Variant names:

• chr17-48614540-C-G
• rs1459891867
• NM_024016.4:c.165G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024016.4(HOXB8):​c.165G>C​(p.Gln55His) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,410 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: HOXB8 NM_024016.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.72
• Publications: 0 publications found

Genes affected

HOXB8 (HGNC:5119): (homeobox B8) This gene is a member of the Antp homeobox family and encodes a nuclear protein with a homeobox DNA-binding domain. It is included in a cluster of homeobox B genes located on chromosome 17. The encoded protein functions as a sequence-specific transcription factor that is involved in development. Increased expression of this gene is associated with colorectal cancer. Mice that have had the murine ortholog of this gene knocked out exhibit an excessive pathologic grooming behavior. This behavior is similar to the behavior of humans suffering from the obsessive-compulsive spectrum disorder trichotillomania. [provided by RefSeq, Jul 2008]

HOXB7 (HGNC:5118): (homeobox B7) This gene is a member of the Antp homeobox family and encodes a protein with a homeobox DNA-binding domain. It is included in a cluster of homeobox B genes located on chromosome 17. The encoded nuclear protein functions as a sequence-specific transcription factor that is involved in cell proliferation and differentiation. Increased expression of this gene is associated with some cases of melanoma and ovarian carcinoma. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024016.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXB8	NM_024016.4	MANE Select	c.165G>C	p.Gln55His	missense	Exon 1 of 2	NP_076921.1	P17481

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXB8	ENST00000239144.5	TSL:2 MANE Select	c.165G>C	p.Gln55His	missense	Exon 1 of 2	ENSP00000239144.4	P17481
	HOXB8	ENST00000884865.1		c.165G>C	p.Gln55His	missense	Exon 4 of 5	ENSP00000554924.1
	HOXB8	ENST00000884866.1		c.165G>C	p.Gln55His	missense	Exon 2 of 3	ENSP00000554925.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000404 AC: 1 AN: 247364 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.00000898

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461410 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 727030

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111844

Other (OTH) AF: 0.00 AC: 0 AN: 60332

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.21	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		5.7
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.21
Sift	Benign	0.091	T
Sift4G	Benign	0.25	T
Polyphen		0.99	D
Vest4		0.57
MutPred		0.31		Gain of phosphorylation at Y58 (P = 0.2521)
MVP		0.80
MPC		1.8
ClinPred		0.78	D
GERP RS		2.7
PromoterAI		0.0022	Neutral
Varity_R		0.34
gMVP		0.77

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: rs1459891867; hg19: chr17-46691902;