rs376040365

Variant names:

• chr17-48529846-G-A
• rs376040365
• NM_002144.4:c.607C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-48529846-G-A
• chr17-48529846-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002144.4(HOXB1):​c.607C>T​(p.Pro203Ser) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HOXB1 NM_002144.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16788831).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXB1	NM_002144.4	c.607C>T	p.Pro203Ser	missense_variant	Exon 2 of 2	ENST00000239174.7	NP_002135.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXB1	ENST00000239174.7	c.607C>T	p.Pro203Ser	missense_variant	Exon 2 of 2	1	NM_002144.4	ENSP00000355140.5
HOXB1	ENST00000577092	c.*360C>T		3_prime_UTR_variant	Exon 1 of 1			ENSP00000459066.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000418 AC: 1 AN: 238952 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 129812

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 SAS exome AF: 0.0000332

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	15
DANN	Benign	0.89
DEOGEN2	Uncertain	0.44	T;T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.71
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.23	.;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Benign	0.32	N;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.7	D;.
REVEL	Benign	0.20
Sift	Uncertain	0.028	D;.
Sift4G	Benign	0.21	T;.
Polyphen		0.0010	B;B
Vest4		0.14
MutPred		0.20		Gain of phosphorylation at P203 (P = 0.0602);Gain of phosphorylation at P203 (P = 0.0602);
MVP		0.88
MPC		0.43
ClinPred		0.054	T
GERP RS		1.6
Varity_R		0.065
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs376040365; hg19: chr17-46607208; COSMIC: COSV53317706;