Variant 7-107189306-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_012257.4(HBP1):c.780T>A(p.Asp260Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,460,250 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 (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

HBP1
NM_012257.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.44

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.33643955).

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HBP1	NM_012257.4 linkuse as main transcript	c.780T>A	p.Asp260Glu	missense_variant	7/11	ENST00000222574.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HBP1	ENST00000222574.9 linkuse as main transcript	c.780T>A	p.Asp260Glu	missense_variant	7/11	1	NM_012257.4	P1	O60381-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1460250

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726472

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 17, 2022

The c.780T>A (p.D260E) alteration is located in exon 7 (coding exon 6) of the HBP1 gene. This alteration results from a T to A substitution at nucleotide position 780, causing the aspartic acid (D) at amino acid position 260 to be replaced by a glutamic acid (E). 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

Benign

0.089

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.010

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

T;T;T;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.062

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.051

MetaRNN

Benign

0.34

T;T;T;T

MetaSVM

Uncertain

0.53

MutationAssessor

Benign

0.97

L;L;L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.15

N;N;N;N

REVEL

Uncertain

0.41

Sift

Benign

0.40

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

B;B;B;.

Vest4

0.32

MutPred

0.62

Gain of ubiquitination at K263 (P = 0.0978);Gain of ubiquitination at K263 (P = 0.0978);Gain of ubiquitination at K263 (P = 0.0978);.;

MVP

0.84

MPC

0.75

ClinPred

0.63

GERP RS

4.8

Varity_R

0.25

gMVP

0.43

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over