5-45286256-T-C

Position:

• chr5-45286256-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_021072.4(HCN1):​c.1618+17343A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0374 in 152,034 control chromosomes in the GnomAD database, including 172 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 0.037 (172 hom., cov: 32)
• Consequence: HCN1 NM_021072.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.161

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]

HCN1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0374 (5680/152034) while in subpopulation NFE AF= 0.0505 (3427/67896). AF 95% confidence interval is 0.0491. There are 172 homozygotes in gnomad4. There are 2921 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 5680 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HCN1	NM_021072.4	c.1618+17343A>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+17343A>G		intron_variant		1	NM_021072.4	ENSP00000307342.4
HCN1	ENST00000673735.1	c.1618+17343A>G		intron_variant				ENSP00000501107.1
HCN1	ENST00000637305.1	n.781+17343A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0374 AC: 5683 AN: 151916 Hom.: 172 Cov.: 32

Gnomad AFR AF: 0.00922

Gnomad AMI AF: 0.0407

Gnomad AMR AF: 0.0218

Gnomad ASJ AF: 0.0479

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00806

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0505

Gnomad OTH AF: 0.0331

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

GnomAD4 genome AF: 0.0374 AC: 5680 AN: 152034 Hom.: 172 Cov.: 32 AF XY: 0.0393 AC XY: 2921 AN XY: 74328

Gnomad4 AFR AF: 0.00920

Gnomad4 AMR AF: 0.0217

Gnomad4 ASJ AF: 0.0479

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00745

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.0505

Gnomad4 OTH AF: 0.0328

Alfa AF: 0.0469 Hom.: 56

Bravo AF: 0.0292

Asia WGS AF: 0.00492 AC: 17 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.63

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: rs17343612; hg19: chr5-45286358;