rs16902086

Positions:

• chr5-45285650-A-G
• chr5-45285650-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.1618+17949T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 151,784 control chromosomes in the GnomAD database, including 18,144 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 0.46 (18144 hom., cov: 32)
• Consequence: HCN1 NM_021072.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HCN1	NM_021072.4	c.1618+17949T>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.1618+17949T>C		intron_variant		1	NM_021072.4	ENSP00000307342	P2
HCN1	ENST00000673735.1	c.1618+17949T>C		intron_variant				ENSP00000501107	A2
HCN1	ENST00000637305.1	n.781+17949T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70435 AN: 151666 Hom.: 18094 Cov.: 32

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.465 AC: 70552 AN: 151784 Hom.: 18144 Cov.: 32 AF XY: 0.468 AC XY: 34692 AN XY: 74180

Gnomad4 AFR AF: 0.698

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.439

Alfa AF: 0.372 Hom.: 18543

Bravo AF: 0.482

Asia WGS AF: 0.521 AC: 1809 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.86
DANN	Benign	0.67

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: rs16902086; hg19: chr5-45285752;