dbSNP rs12522910: HCN1:c.*2660A>G (chr5-45259261-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021072.4(HCN1):c.*2660A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 151,810 control chromosomes in the GnomAD database, including 1,953 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 1953 hom., cov: 32)

Exomes 𝑓: 0.13 ( 0 hom. )

Consequence

HCN1
NM_021072.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.230

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy, 24
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
generalized epilepsy with febrile seizures plus
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
generalized epilepsy with febrile seizures plus, type 10
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
undetermined early-onset epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

HCN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HCN1	NM_021072.4 link	c.*2660A>G		3_prime_UTR_variant	Exon 8 of 8	ENST00000303230.6	NP_066550.2	O60741Q86WJ6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
HCN1	ENST00000303230.6 link	c.*2660A>G	3_prime_UTR_variant	Exon 8 of 8	1	NM_021072.4	ENSP00000307342.4	O60741
HCN1	ENST00000673735.1 link	c.*3558A>G	3_prime_UTR_variant	Exon 9 of 9			ENSP00000501107.1	A0A669KB45
HCN1	ENST00000637305.1 link	n.*196A>G	downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.148

AC:

22420

AN:

151672

Hom.:

1957

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0628

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.231

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.115

Gnomad SAS

AF:

0.196

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.163

GnomAD4 exome

AF:

0.125

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.125

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.148

AC:

22411

AN:

151786

Hom.:

1953

Cov.:

AF XY:

0.150

AC XY:

11117

AN XY:

74200

show subpopulations

African (AFR)

AF:

0.0627

AC:

2604

AN:

41518

American (AMR)

AF:

0.230

AC:

3514

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.276

AC:

955

AN:

3466

East Asian (EAS)

AF:

0.115

AC:

596

AN:

5162

South Asian (SAS)

AF:

0.196

AC:

946

AN:

4828

European-Finnish (FIN)

AF:

0.136

AC:

1414

AN:

10434

Middle Eastern (MID)

AF:

0.233

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.175

AC:

11851

AN:

67824

Other (OTH)

AF:

0.160

AC:

337

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

980

1959

2939

3918

4898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

262

524

786

1048

1310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.156

Hom.:

251

Bravo

AF:

0.152

Asia WGS

AF:

0.156

AC:

533

AN:

3426

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.78

PhyloP100

0.23

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over