chr17-48530596-T-G

Variant names:

• chr17-48530596-T-G
• rs12939811
• NM_002144.4:c.309A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002144.4(HOXB1):​c.309A>C​(p.Gln103His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HOXB1 NM_002144.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 37 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11657041).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXB1	NM_002144.4	c.309A>C	p.Gln103His	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.309A>C	p.Gln103His	missense_variant	Exon 1 of 2	1	NM_002144.4	ENSP00000355140.5
HOXB1	ENST00000577092.1	c.309A>C	p.Gln103His	missense_variant	Exon 1 of 1	6		ENSP00000459066.1
ENSG00000294508	ENST00000724000.1	n.817+2223T>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1858

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	5.6
DANN	Benign	0.82
DEOGEN2	Benign	0.22	T;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.45	.;T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.37	T
MutationAssessor	Benign	1.8	L;L;L
PhyloP100		-1.4
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.3	N;.;.
REVEL	Uncertain	0.36
Sift	Uncertain	0.015	D;.;.
Sift4G	Benign	0.077	T;.;D
Polyphen		0.64	P;P;.
Vest4		0.26
MutPred		0.10		Gain of catalytic residue at Q103 (P = 0.0787);Gain of catalytic residue at Q103 (P = 0.0787);Gain of catalytic residue at Q103 (P = 0.0787);
MVP		0.58
MPC		0.71
ClinPred		0.52	D
GERP RS		-5.7
PromoterAI		0.0085	Neutral
Varity_R		0.13
gMVP		0.48

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: rs12939811; hg19: chr17-46607958;