rs12522910

chr5-45259261-T-C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230

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=-0.53).
• 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/exons	MANE	UniProt
HCN1	NM_021072.4	c.*2660A>G		3_prime_UTR_variant	8/8	ENST00000303230.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HCN1	ENST00000303230.6	c.*2660A>G		3_prime_UTR_variant	8/8	1	NM_021072.4	P2
HCN1	ENST00000673735.1	c.*3558A>G		3_prime_UTR_variant	9/9			A2

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22420 AN: 151672 Hom.: 1957 Cov.: 32

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: 3 AN: 24 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 10

Gnomad4 FIN exome AF: 0.125

GnomAD4 genome AF: 0.148 AC: 22411 AN: 151786 Hom.: 1953 Cov.: 32 AF XY: 0.150 AC XY: 11117 AN XY: 74200

Gnomad4 AFR AF: 0.0627

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.160

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	11
Dann	Benign	0.78

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: rs12522910; hg19: chr5-45259363;