rs16902083

Positions:

• chr5-45282706-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.1619-15453T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,172 control chromosomes in the GnomAD database, including 2,113 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 0.15 (2113 hom., cov: 32)
• Consequence: HCN1 NM_021072.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142

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 (AMR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HCN1	NM_021072.4	c.1619-15453T>G		intron_variant		ENST00000303230.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HCN1	ENST00000303230.6	c.1619-15453T>G		intron_variant		1	NM_021072.4	P2
HCN1	ENST00000673735.1	c.1619-15453T>G		intron_variant				A2
HCN1	ENST00000637305.1	n.782-15453T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23471 AN: 152054 Hom.: 2117 Cov.: 32

Gnomad AFR AF: 0.0647

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.154 AC: 23464 AN: 152172 Hom.: 2113 Cov.: 32 AF XY: 0.156 AC XY: 11629 AN XY: 74392

Gnomad4 AFR AF: 0.0646

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.168

Alfa AF: 0.167 Hom.: 370

Bravo AF: 0.158

Asia WGS AF: 0.159 AC: 550 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	0.040
DANN	Benign	0.38

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: rs16902083; hg19: chr5-45282808;