rs2337954

Positions:

• chr5-45651767-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021072.4(HCN1):​c.426-6159C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 151,634 control chromosomes in the GnomAD database, including 5,694 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 0.27 (5694 hom., cov: 31)
• Consequence: HCN1 NM_021072.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.251

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 = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HCN1	NM_021072.4	c.426-6159C>T		intron_variant		ENST00000303230.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HCN1	ENST00000303230.6	c.426-6159C>T		intron_variant		1	NM_021072.4	P2
HCN1	ENST00000634658.1	c.426-6159C>T		intron_variant		3
HCN1	ENST00000673735.1	c.426-6159C>T		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41138 AN: 151516 Hom.: 5688 Cov.: 31

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.272 AC: 41172 AN: 151634 Hom.: 5694 Cov.: 31 AF XY: 0.269 AC XY: 19970 AN XY: 74112

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.323

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.265

Alfa AF: 0.264 Hom.: 864

Bravo AF: 0.273

Asia WGS AF: 0.292 AC: 1013 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.7
DANN	Benign	0.38

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: rs2337954; hg19: chr5-45651869;