rs17293295

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
HCN1	NM_021072.4	c.850-47466C>T		intron_variant		ENST00000303230.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HCN1	ENST00000303230.6	c.850-47466C>T		intron_variant		1	NM_021072.4	P2
HCN1	ENST00000673735.1	c.850-47466C>T		intron_variant				A2

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

Gnomad4 AFR AF: 0.259

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.231

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

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

Other links and lift over

dbSNP: rs17293295; hg19: chr5-45509575;