chr5-45265666-T-C

Position:

• chr5-45265666-T-C

Variant summary

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

The NM_021072.4(HCN1):​c.1783+1423A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,174 control chromosomes in the GnomAD database, including 1,456 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 0.12 (1456 hom., cov: 32)
• Consequence: HCN1 NM_021072.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HCN1	NM_021072.4	c.1783+1423A>G		intron_variant		ENST00000303230.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HCN1	ENST00000303230.6	c.1783+1423A>G		intron_variant		1	NM_021072.4	P2
HCN1	ENST00000673735.1	c.*8+849A>G		intron_variant				A2
HCN1	ENST00000637305.1	n.946+1423A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18751 AN: 152056 Hom.: 1449 Cov.: 32

Gnomad AFR AF: 0.0781

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.123 AC: 18778 AN: 152174 Hom.: 1456 Cov.: 32 AF XY: 0.129 AC XY: 9566 AN XY: 74404

Gnomad4 AFR AF: 0.0780

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.131

Alfa AF: 0.119 Hom.: 2367

Bravo AF: 0.120

Asia WGS AF: 0.281 AC: 977 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.4
DANN	Benign	0.75

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: rs13180087; hg19: chr5-45265768;