rs7164883

chr15-73359833-A-G

Variant summary

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

The NM_005477.3(HCN4):c.785+7653T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,132 control chromosomes in the GnomAD database, including 3,791 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 0.21 (3791 hom., cov: 32)
• Consequence: HCN4 NM_005477.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.366

Genes affected

HCN4 (HGNC:16882): (hyperpolarization activated cyclic nucleotide gated potassium channel 4) This gene encodes a member of the hyperpolarization-activated cyclic nucleotide-gated potassium channels. The encoded protein shows slow kinetics of activation and inactivation, and is necessary for the cardiac pacemaking process. This channel may also mediate responses to sour stimuli. Mutations in this gene have been linked to sick sinus syndrome 2, also known as atrial fibrillation with bradyarrhythmia or familial sinus bradycardia. Two pseudogenes have been identified on chromosome 15. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HCN4	NM_005477.3	c.785+7653T>C		intron_variant		ENST00000261917.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HCN4	ENST00000261917.4	c.785+7653T>C		intron_variant		1	NM_005477.3	P1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31871 AN: 152014 Hom.: 3774 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.210 AC: 31929 AN: 152132 Hom.: 3791 Cov.: 32 AF XY: 0.210 AC XY: 15612 AN XY: 74370

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.192

Alfa AF: 0.169 Hom.: 3643

Bravo AF: 0.212

Asia WGS AF: 0.137 AC: 474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.67
Dann	Benign	0.73

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: rs7164883; hg19: chr15-73652174;