rs1483307

chr5-45491837-A-Gchr5-45491837-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.850-29830T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,014 control chromosomes in the GnomAD database, including 11,756 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 0.35 (11756 hom., cov: 32)
• Consequence: HCN1 NM_021072.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258

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).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HCN1	NM_021072.4	c.850-29830T>C		intron_variant		ENST00000303230.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HCN1	ENST00000303230.6	c.850-29830T>C		intron_variant		1	NM_021072.4	P2
HCN1	ENST00000673735.1	c.850-29830T>C		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52758 AN: 151896 Hom.: 11752 Cov.: 32

Gnomad AFR AF: 0.0798

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.347 AC: 52764 AN: 152014 Hom.: 11756 Cov.: 32 AF XY: 0.352 AC XY: 26151 AN XY: 74260

Gnomad4 AFR AF: 0.0796

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.380

Alfa AF: 0.434 Hom.: 14629

Bravo AF: 0.325

Asia WGS AF: 0.279 AC: 973 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.5
Dann	Benign	0.54

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: rs1483307; hg19: chr5-45491939;