rs13163424

Positions:

• chr5-45419486-C-T

Variant summary

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

The NM_021072.4(HCN1):​c.1012-22776G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0303 in 152,272 control chromosomes in the GnomAD database, including 103 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 0.030 (103 hom., cov: 31)
• Consequence: HCN1 NM_021072.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0303 (4612/152272) while in subpopulation NFE AF= 0.045 (3062/68022). AF 95% confidence interval is 0.0437. There are 103 homozygotes in gnomad4. There are 2126 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4612 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HCN1	NM_021072.4	c.1012-22776G>A		intron_variant		ENST00000303230.6	NP_066550.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HCN1	ENST00000303230.6	c.1012-22776G>A		intron_variant		1	NM_021072.4	ENSP00000307342.4
HCN1	ENST00000673735.1	c.1012-22776G>A		intron_variant				ENSP00000501107.1
HCN1	ENST00000637305.1	n.175-22776G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0303 AC: 4610 AN: 152154 Hom.: 103 Cov.: 31

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0291

Gnomad ASJ AF: 0.0643

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0269

Gnomad FIN AF: 0.0180

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0450

Gnomad OTH AF: 0.0320

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

GnomAD4 genome AF: 0.0303 AC: 4612 AN: 152272 Hom.: 103 Cov.: 31 AF XY: 0.0286 AC XY: 2126 AN XY: 74450

Gnomad4 AFR AF: 0.0103

Gnomad4 AMR AF: 0.0290

Gnomad4 ASJ AF: 0.0643

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0272

Gnomad4 FIN AF: 0.0180

Gnomad4 NFE AF: 0.0450

Gnomad4 OTH AF: 0.0321

Alfa AF: 0.0380 Hom.: 33

Bravo AF: 0.0305

Asia WGS AF: 0.0140 AC: 49 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	3.1
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs13163424; hg19: chr5-45419588;