rs6451793

Positions:

• chr5-45277010-A-G
• chr5-45277010-A-T

Variant summary

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

The NM_021072.4(HCN1):​c.1619-9757T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 151,904 control chromosomes in the GnomAD database, including 7,016 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 0.28 (7016 hom., cov: 32)
• Consequence: HCN1 NM_021072.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.409

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HCN1	NM_021072.4	c.1619-9757T>C		intron_variant		ENST00000303230.6	NP_066550.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HCN1	ENST00000303230.6	c.1619-9757T>C		intron_variant		1	NM_021072.4	ENSP00000307342.4
HCN1	ENST00000673735.1	c.1619-9757T>C		intron_variant				ENSP00000501107.1
HCN1	ENST00000637305.1	n.782-9757T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41791 AN: 151786 Hom.: 6987 Cov.: 32

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.276 AC: 41875 AN: 151904 Hom.: 7016 Cov.: 32 AF XY: 0.274 AC XY: 20353 AN XY: 74260

Gnomad4 AFR AF: 0.469

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.255

Alfa AF: 0.207 Hom.: 7314

Bravo AF: 0.296

Asia WGS AF: 0.203 AC: 704 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.42
DANN	Benign	0.76

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: rs6451793; hg19: chr5-45277112;