chr7-107179923-G-C

Variant names:

• chr7-107179923-G-C
• rs779971042
• NM_012257.4:c.30G>C

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.30G>C​(p.Met10Ile) 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. 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 Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M10L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HBP1 NM_012257.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.78
• Publications: 2 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=0.25139287).

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.30G>C	p.Met10Ile	missense	Exon 2 of 11	NP_036389.2
	HBP1	NM_001244262.2		c.60G>C	p.Met20Ile	missense	Exon 2 of 11	NP_001231191.1	B4DJ36
	HBP1	NM_001439011.1		c.30G>C	p.Met10Ile	missense	Exon 3 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.30G>C	p.Met10Ile	missense	Exon 2 of 11	ENSP00000222574.4	O60381-1
	HBP1	ENST00000463202.5	TSL:1	n.46G>C		non_coding_transcript_exon	Exon 1 of 9
	HBP1	ENST00000895664.1		c.30G>C	p.Met10Ile	missense	Exon 2 of 11	ENSP00000565723.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.16	T
Eigen	Benign	0.080
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.78	D
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.25	T
MetaSVM	Uncertain	0.66	D
MutationAssessor	Benign	1.0	L
PhyloP100		5.8
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.78	N
REVEL	Uncertain	0.46
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.070	T
Polyphen		0.0090	B
Vest4		0.55
MutPred		0.26		Loss of disorder (P = 0.0523)
MVP		0.76
MPC		0.041
ClinPred		0.55	D
GERP RS		5.9
PromoterAI		-0.0066	Neutral
Varity_R		0.34
gMVP		0.21
Mutation Taster		=57/43	polymorphism

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

Other links and lift over

dbSNP: rs779971042; hg19: chr7-106820368;