chr7-107185827-C-G

Variant names:

• chr7-107185827-C-G
• NM_012257.4:c.425C>G

Variant summary

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

The NM_012257.4(HBP1):​c.425C>G​(p.Thr142Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar 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: 4.58
• Publications: 0 publications found

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

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=0.22771913).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012257.4. 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
	HBP1	NM_012257.4	MANE Select	c.425C>G	p.Thr142Ser	missense	Exon 4 of 11	NP_036389.2
	HBP1	NM_001244262.2		c.455C>G	p.Thr152Ser	missense	Exon 4 of 11	NP_001231191.1	B4DJ36
	HBP1	NM_001439011.1		c.425C>G	p.Thr142Ser	missense	Exon 5 of 12	NP_001425940.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBP1	ENST00000222574.9	TSL:1 MANE Select	c.425C>G	p.Thr142Ser	missense	Exon 4 of 11	ENSP00000222574.4	O60381-1
	HBP1	ENST00000463202.5	TSL:1	n.441C>G		non_coding_transcript_exon	Exon 3 of 9
	HBP1	ENST00000895664.1		c.440C>G	p.Thr147Ser	missense	Exon 4 of 11	ENSP00000565723.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

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	Benign	0.18
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.0098
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.23	T
MetaSVM	Uncertain	0.61	D
MutationAssessor	Benign	1.0	L
PhyloP100		4.6
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.76	N
REVEL	Uncertain	0.45
Sift	Benign	0.25	T
Sift4G	Benign	0.71	T
Polyphen		0.013	B
Vest4		0.18
MutPred		0.15		Loss of sheet (P = 0.0817)
MVP		0.67
MPC		0.040
ClinPred		0.62	D
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.33
Mutation Taster		=95/5	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

Other links and lift over

hg19: chr7-106826272;