chr5-45448478-C-G

Position:

• chr5-45448478-C-G

Variant summary

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

The NM_021072.4(HCN1):​c.1011+13368G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0686 in 152,264 control chromosomes in the GnomAD database, including 448 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 0.069 (448 hom., cov: 32)
• Consequence: HCN1 NM_021072.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.347

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 (EAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HCN1	NM_021072.4	c.1011+13368G>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.1011+13368G>C		intron_variant		1	NM_021072.4	ENSP00000307342	P2
HCN1	ENST00000673735.1	c.1011+13368G>C		intron_variant				ENSP00000501107	A2
HCN1	ENST00000637305.1	n.174+13368G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0685 AC: 10424 AN: 152146 Hom.: 444 Cov.: 32

Gnomad AFR AF: 0.0892

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0991

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.0664

Gnomad FIN AF: 0.0511

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0499

Gnomad OTH AF: 0.0555

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

GnomAD4 genome AF: 0.0686 AC: 10452 AN: 152264 Hom.: 448 Cov.: 32 AF XY: 0.0695 AC XY: 5175 AN XY: 74448

Gnomad4 AFR AF: 0.0895

Gnomad4 AMR AF: 0.0993

Gnomad4 ASJ AF: 0.0213

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.0658

Gnomad4 FIN AF: 0.0511

Gnomad4 NFE AF: 0.0499

Gnomad4 OTH AF: 0.0554

Alfa AF: 0.0663 Hom.: 53

Bravo AF: 0.0768

Asia WGS AF: 0.134 AC: 466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.75
DANN	Benign	0.64

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: rs6875925; hg19: chr5-45448580;