Variant rs1060500095 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_ModerateBP6_ModerateBS2

The NM_021072.4(HCN1):c.128C>T(p.Pro43Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000702 in 1,324,668 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000077 ( 0 hom. )

Consequence

HCN1
NM_021072.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.32

Variant links:

Genes affected

HCN1 (HGNC:4845): (hyperpolarization activated cyclic nucleotide gated potassium channel 1) The membrane protein encoded by this gene is a hyperpolarization-activated cation channel that contributes to the native pacemaker currents in heart and neurons. The encoded protein can homodimerize or heterodimerize with other pore-forming subunits to form a potassium channel. This channel may act as a receptor for sour tastes. [provided by RefSeq, Oct 2011]

HCN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), HCN1. . Gene score misZ 3.6647 (greater than the threshold 3.09). Trascript score misZ 3.2427 (greater than threshold 3.09). GenCC has associacion of gene with generalized epilepsy with febrile seizures plus, type 10, undetermined early-onset epileptic encephalopathy, developmental and epileptic encephalopathy, 24, generalized epilepsy with febrile seizures plus.

BP4

Computational evidence support a benign effect (MetaRNN=0.19371226).

BP6

Variant 5-45695966-G-A is Benign according to our data. Variant chr5-45695966-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 404096.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 91 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HCN1	NM_021072.4 linkuse as main transcript	c.128C>T	p.Pro43Leu	missense_variant	1/8	ENST00000303230.6	NP_066550.2	O60741Q86WJ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HCN1	ENST00000303230.6 linkuse as main transcript	c.128C>T	p.Pro43Leu	missense_variant	1/8	1	NM_021072.4	ENSP00000307342.4	O60741
HCN1	ENST00000673735.1 linkuse as main transcript	c.128C>T	p.Pro43Leu	missense_variant	1/9			ENSP00000501107.1	A0A669KB45
HCN1	ENST00000634658.1 linkuse as main transcript	c.128C>T	p.Pro43Leu	missense_variant	1/2	3		ENSP00000489134.1	A0A0U1RQR7

Frequencies

GnomAD3 genomes

AF:

0.0000134

AC:

AN:

149498

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000297

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000431

AC:

AN:

23184

Hom.:

AF XY:

0.00

AC XY:

AN XY:

14862

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000933

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000774

AC:

AN:

1175170

Hom.:

Cov.:

AF XY:

0.0000733

AC XY:

AN XY:

573228

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:

0.0000910

Gnomad4 OTH exome

AF:

0.0000423

GnomAD4 genome

AF:

0.0000134

AC:

AN:

149498

Hom.:

Cov.:

AF XY:

0.0000274

AC XY:

AN XY:

72898

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000297

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Early infantile epileptic encephalopathy with suppression bursts

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 17, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Uncertain

0.037

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

T;T

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.095

LIST_S2

Benign

0.63

T;T

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.19

T;T

MetaSVM

Uncertain

0.0068

MutationAssessor

Benign

-0.34

N;.

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.9

N;.

REVEL

Benign

0.29

Sift

Uncertain

0.013

D;.

Sift4G

Uncertain

0.0080

D;T

Polyphen

0.043

B;.

Vest4

0.16

MutPred

0.16

Loss of relative solvent accessibility (P = 0.0676);Loss of relative solvent accessibility (P = 0.0676);

MVP

0.61

MPC

2.4

ClinPred

0.19

GERP RS

3.0

Varity_R

0.14

gMVP

0.21

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