Variant rs483352934 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBA1

The NM_021072.4(HCN1):c.201_209del(p.Gly72_Gly74del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0212 in 1,529,748 control chromosomes in the GnomAD database, including 621 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 87 hom., cov: 32)

Exomes 𝑓: 0.020 ( 534 hom. )

Consequence

HCN1
NM_021072.4 inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.38

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 -14 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_021072.4.

BP6

Variant 5-45695884-GCCGCCGCCA-G is Benign according to our data. Variant chr5-45695884-GCCGCCGCCA-G is described in ClinVar as [Benign]. Clinvar id is 95999.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-45695884-GCCGCCGCCA-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HCN1	NM_021072.4 linkuse as main transcript	c.201_209del	p.Gly72_Gly74del	inframe_deletion	1/8	ENST00000303230.6	NP_066550.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
HCN1	ENST00000303230.6 linkuse as main transcript	c.201_209del	p.Gly72_Gly74del	inframe_deletion	1/8	1	NM_021072.4	ENSP00000307342	P2
HCN1	ENST00000634658.1 linkuse as main transcript	c.201_209del	p.Gly72_Gly74del	inframe_deletion	1/2	3		ENSP00000489134
HCN1	ENST00000673735.1 linkuse as main transcript	c.201_209del	p.Gly72_Gly74del	inframe_deletion	1/9			ENSP00000501107	A2

Frequencies

GnomAD3 genomes

AF:

0.0284

AC:

4277

AN:

150482

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0621

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0166

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.000398

Gnomad SAS

AF:

0.0207

Gnomad FIN

AF:

0.00774

Gnomad MID

AF:

0.0321

Gnomad NFE

AF:

0.0181

Gnomad OTH

AF:

0.0222

GnomAD3 exomes

AF:

0.0198

AC:

2842

AN:

143504

Hom.:

140

AF XY:

0.0205

AC XY:

1633

AN XY:

79598

show subpopulations

Gnomad AFR exome

AF:

0.0798

Gnomad AMR exome

AF:

0.0117

Gnomad ASJ exome

AF:

0.00239

Gnomad EAS exome

AF:

0.000429

Gnomad SAS exome

AF:

0.0323

Gnomad FIN exome

AF:

0.00688

Gnomad NFE exome

AF:

0.0195

Gnomad OTH exome

AF:

0.0200

GnomAD4 exome

AF:

0.0204

AC:

28203

AN:

1379162

Hom.:

534

AF XY:

0.0205

AC XY:

14004

AN XY:

681950

show subpopulations

Gnomad4 AFR exome

AF:

0.0643

Gnomad4 AMR exome

AF:

0.0132

Gnomad4 ASJ exome

AF:

0.00156

Gnomad4 EAS exome

AF:

0.000165

Gnomad4 SAS exome

AF:

0.0289

Gnomad4 FIN exome

AF:

0.00701

Gnomad4 NFE exome

AF:

0.0203

Gnomad4 OTH exome

AF:

0.0209

GnomAD4 genome

AF:

0.0284

AC:

4280

AN:

150586

Hom.:

Cov.:

AF XY:

0.0264

AC XY:

1942

AN XY:

73588

show subpopulations

Gnomad4 AFR

AF:

0.0619

Gnomad4 AMR

AF:

0.0166

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.000399

Gnomad4 SAS

AF:

0.0216

Gnomad4 FIN

AF:

0.00774

Gnomad4 NFE

AF:

0.0181

Gnomad4 OTH

AF:

0.0219

Alfa

AF:

0.00609

Hom.:

Asia WGS

AF:

0.0110

AC:

AN:

3400

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Mar 08, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 02, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Aug 12, 2013

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 13, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Early infantile epileptic encephalopathy with suppression bursts

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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