Genetic Variant NM_012257.4:c.30G>A (chr7-107179923-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012257.4(HBP1):c.30G>A(p.Met10Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000281 in 1,424,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. M10L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

HBP1
NM_012257.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.78

Publications

2 publications found

Variant links:

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]

HBP1 links:

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ACMG classification

Classification was made for transcript

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=0.23450223).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HBP1	NM_012257.4	MANE Select	c.30G>A	p.Met10Ile	missense	Exon 2 of 11	NP_036389.2
HBP1	NM_001244262.2		c.60G>A	p.Met20Ile	missense	Exon 2 of 11	NP_001231191.1	B4DJ36
HBP1	NM_001439011.1		c.30G>A	p.Met10Ile	missense	Exon 3 of 12	NP_001425940.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HBP1	ENST00000222574.9	TSL:1 MANE Select	c.30G>A	p.Met10Ile	missense	Exon 2 of 11	ENSP00000222574.4	O60381-1
HBP1	ENST00000463202.5	TSL:1	n.46G>A		non_coding_transcript_exon	Exon 1 of 9
HBP1	ENST00000895664.1		c.30G>A	p.Met10Ile	missense	Exon 2 of 11	ENSP00000565723.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251372

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000281

AC:

AN:

1424562

Hom.:

Cov.:

AF XY:

0.00000424

AC XY:

AN XY:

708352

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32342

American (AMR)

AF:

0.00

AC:

AN:

43932

Ashkenazi Jewish (ASJ)

AF:

0.0000402

AC:

AN:

24846

East Asian (EAS)

AF:

0.00

AC:

AN:

37772

South Asian (SAS)

AF:

0.00

AC:

AN:

85602

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50968

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5596

European-Non Finnish (NFE)

AF:

0.00000276

AC:

AN:

1085388

Other (OTH)

AF:

0.00

AC:

AN:

58116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.16

Eigen

Benign

0.080

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.89

M_CAP

Benign

0.060

MetaRNN

Benign

0.23

MetaSVM

Uncertain

0.66

MutationAssessor

Benign

1.0

PhyloP100

5.8

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.78

REVEL

Uncertain

0.46

Sift

Uncertain

0.0070

Sift4G

Benign

0.070

Polyphen

0.0090

Vest4

0.55

MutPred

0.26

Loss of disorder (P = 0.0523)

MVP

0.75

MPC

0.041

ClinPred

0.46

GERP RS

5.9

PromoterAI

-0.023

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.34

gMVP

0.21

Mutation Taster

=57/43

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over