7-107185854-G-C

Variant names:

• chr7-107185854-G-C
• NM_012257.4:c.452G>C

Variant summary

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

The NM_012257.4(HBP1):​c.452G>C​(p.Arg151Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R151C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HBP1 NM_012257.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.54

Genes affected

HBP1 (HGNC:23200): (HMG-box transcription factor 1) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of lipid transport; negative regulation of reactive oxygen species biosynthetic process; and negative regulation of transcription by RNA polymerase II. Located in nuclear speck. Biomarker of osteoarthritis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HBP1	NM_012257.4	c.452G>C	p.Arg151Pro	missense_variant	Exon 4 of 11	ENST00000222574.9	NP_036389.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HBP1	ENST00000222574.9	c.452G>C	p.Arg151Pro	missense_variant	Exon 4 of 11	1	NM_012257.4	ENSP00000222574.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.452G>C (p.R151P) alteration is located in exon 4 (coding exon 3) of the HBP1 gene. This alteration results from a G to C substitution at nucleotide position 452, causing the arginine (R) at amino acid position 151 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.52	D
BayesDel_noAF	Pathogenic	0.50
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;T;T;T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Pathogenic	1.0	D
M_CAP	Uncertain	0.24	D
MetaRNN	Uncertain	0.64	D;D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Benign	1.0	L;L;L;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.80	N;N;N;N
REVEL	Uncertain	0.55
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.0040	D;D;D;D
Polyphen		1.0	D;D;D;.
Vest4		0.83
MutPred		0.30		Gain of glycosylation at R151 (P = 0.0071);Gain of glycosylation at R151 (P = 0.0071);Gain of glycosylation at R151 (P = 0.0071);.;
MVP		0.81
MPC		0.31
ClinPred		0.94	D
GERP RS		6.2
Varity_R		0.51
gMVP		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.24		Position offset: 12

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-106826299;