rs12374423

chr5-45530520-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_021072.4(HCN1):c.850-68513G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0217 in 151,166 control chromosomes in the GnomAD database, including 67 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 0.022 (67 hom., cov: 31)
• Consequence: HCN1 NM_021072.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.730

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=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0217 (3287/151166) while in subpopulation NFE AF= 0.0306 (2075/67802). AF 95% confidence interval is 0.0295. There are 67 homozygotes in gnomad4. There are 1644 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 3287 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HCN1	NM_021072.4	c.850-68513G>T		intron_variant		ENST00000303230.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HCN1	ENST00000303230.6	c.850-68513G>T		intron_variant		1	NM_021072.4	P2
HCN1	ENST00000673735.1	c.850-68513G>T		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.0218 AC: 3287 AN: 151064 Hom.: 67 Cov.: 31

Gnomad AFR AF: 0.00445

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.0234

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00146

Gnomad FIN AF: 0.0670

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.0306

Gnomad OTH AF: 0.0207

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

GnomAD4 genome AF: 0.0217 AC: 3287 AN: 151166 Hom.: 67 Cov.: 31 AF XY: 0.0223 AC XY: 1644 AN XY: 73800

Gnomad4 AFR AF: 0.00441

Gnomad4 AMR AF: 0.0120

Gnomad4 ASJ AF: 0.0234

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00167

Gnomad4 FIN AF: 0.0670

Gnomad4 NFE AF: 0.0306

Gnomad4 OTH AF: 0.0205

Alfa AF: 0.0279 Hom.: 22

Bravo AF: 0.0172

Asia WGS AF: 0.00203 AC: 7 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.99
Dann	Benign	0.44

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: rs12374423; hg19: chr5-45530622;