chr5-45285616-A-C

Position:

• chr5-45285616-A-C

Variant summary

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

The NM_021072.4(HCN1):​c.1618+17983T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,870 control chromosomes in the GnomAD database, including 11,283 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 0.34 (11283 hom., cov: 32)
• Consequence: HCN1 NM_021072.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.654

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=-0.56).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HCN1	NM_021072.4	c.1618+17983T>G		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+17983T>G		intron_variant		1	NM_021072.4	ENSP00000307342	P2
HCN1	ENST00000673735.1	c.1618+17983T>G		intron_variant				ENSP00000501107	A2
HCN1	ENST00000637305.1	n.781+17983T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52268 AN: 151752 Hom.: 11285 Cov.: 32

Gnomad AFR AF: 0.0845

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.344 AC: 52266 AN: 151870 Hom.: 11283 Cov.: 32 AF XY: 0.344 AC XY: 25540 AN XY: 74172

Gnomad4 AFR AF: 0.0842

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.403

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.553

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.382

Alfa AF: 0.423 Hom.: 13133

Bravo AF: 0.328

Asia WGS AF: 0.256 AC: 894 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.70

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: rs981782; hg19: chr5-45285718; COSMIC: COSV57495154;