Variant chr17-2057486-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006497.4(HIC1):c.796G>A(p.Ala266Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000924 in 1,483,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00097 ( 0 hom. )

Consequence

HIC1
NM_006497.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.13

Variant links:

Genes affected

HIC1 (HGNC:4909): (HIC ZBTB transcriptional repressor 1) This gene functions as a growth regulatory and tumor repressor gene. Hypermethylation or deletion of the region of this gene have been associated with tumors and the contiguous-gene syndrome, Miller-Dieker syndrome. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2010]

HIC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013625175).

BS2

High AC in GnomAd4 at 83 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIC1	NM_006497.4 linkuse as main transcript	c.796G>A	p.Ala266Thr	missense_variant	2/2	ENST00000619757.5	NP_006488.2
HIC1	NM_001098202.1 linkuse as main transcript	c.853G>A	p.Ala285Thr	missense_variant	2/2		NP_001091672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIC1	ENST00000619757.5 linkuse as main transcript	c.796G>A	p.Ala266Thr	missense_variant	2/2	1	NM_006497.4	ENSP00000477858	P4	Q14526-2
HIC1	ENST00000399849.4 linkuse as main transcript	c.796G>A	p.Ala266Thr	missense_variant	2/2	1		ENSP00000382742	P4	Q14526-2
HIC1	ENST00000322941.3 linkuse as main transcript	c.853G>A	p.Ala285Thr	missense_variant	2/2	5		ENSP00000314080	A1	Q14526-1

Frequencies

GnomAD3 genomes

AF:

0.000547

AC:

AN:

151848

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000191

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000957

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000481

AC:

AN:

85186

Hom.:

AF XY:

0.000455

AC XY:

AN XY:

48332

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000543

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000112

Gnomad FIN exome

AF:

0.000603

Gnomad NFE exome

AF:

0.00114

Gnomad OTH exome

AF:

0.000395

GnomAD4 exome

AF:

0.000967

AC:

1287

AN:

1331502

Hom.:

Cov.:

AF XY:

0.000911

AC XY:

598

AN XY:

656446

show subpopulations

Gnomad4 AFR exome

AF:

0.0000373

Gnomad4 AMR exome

AF:

0.0000335

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000268

Gnomad4 FIN exome

AF:

0.000515

Gnomad4 NFE exome

AF:

0.00117

Gnomad4 OTH exome

AF:

0.000615

GnomAD4 genome

AF:

0.000547

AC:

AN:

151848

Hom.:

Cov.:

AF XY:

0.000512

AC XY:

AN XY:

74158

show subpopulations

Gnomad4 AFR

AF:

0.000314

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000191

Gnomad4 NFE

AF:

0.000957

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000654

Hom.:

Bravo

AF:

0.000499

ExAC

AF:

0.000227

AC:

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

Oct 12, 2021

The c.853G>A (p.A285T) alteration is located in exon 2 (coding exon 2) of the HIC1 gene. This alteration results from a G to A substitution at nucleotide position 853, causing the alanine (A) at amino acid position 285 to be replaced by a threonine (T). 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

0.11

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.66

DANN

Benign

0.95

DEOGEN2

Benign

0.15

.;.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.38

T;.;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.014

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

.;.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.31

N;.;N

REVEL

Benign

0.020

Sift

Benign

0.56

T;.;T

Sift4G

Benign

0.62

T;T;T

Polyphen

0.0010

.;.;B

Vest4

0.027

MVP

0.072

ClinPred

0.016

GERP RS

-6.1

Varity_R

0.041

gMVP

0.11

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