rs17293295

Variant names:

• chr5-45509473-G-A
• rs17293295
• NM_021072.4:c.850-47466C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-45509473-G-A
• chr5-45509473-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021072.4(HCN1):​c.850-47466C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,038 control chromosomes in the GnomAD database, including 4,677 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 0.24 (4677 hom., cov: 33)
• Consequence: HCN1 NM_021072.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.720
• Publications: 1 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HCN1	NM_021072.4	c.850-47466C>T		intron_variant	Intron 2 of 7	ENST00000303230.6	NP_066550.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HCN1	ENST00000303230.6	c.850-47466C>T		intron_variant	Intron 2 of 7	1	NM_021072.4	ENSP00000307342.4
HCN1	ENST00000673735.1	c.850-47466C>T		intron_variant	Intron 2 of 8			ENSP00000501107.1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37197 AN: 151920 Hom.: 4672 Cov.: 33

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.229

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.245 AC: 37228 AN: 152038 Hom.: 4677 Cov.: 33 AF XY: 0.243 AC XY: 18083 AN XY: 74336

African (AFR) AF: 0.259 AC: 10756 AN: 41496

American (AMR) AF: 0.226 AC: 3456 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 849 AN: 3466

East Asian (EAS) AF: 0.322 AC: 1661 AN: 5162

South Asian (SAS) AF: 0.297 AC: 1428 AN: 4808

European-Finnish (FIN) AF: 0.190 AC: 2008 AN: 10584

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16181 AN: 67944

Other (OTH) AF: 0.231 AC: 488 AN: 2112

Alfa AF: 0.233 Hom.: 677

Bravo AF: 0.247

Asia WGS AF: 0.286 AC: 993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.067
DANN	Benign	0.60
PhyloP100		-0.72
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17293295; hg19: chr5-45509575;