rs11264351

Positions:

• chr1-155283704-G-A
• chr1-155283704-G-C
• chr1-155283704-G-T

Variant summary

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

The NM_020897.3(HCN3):​c.709-270G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0592 in 152,022 control chromosomes in the GnomAD database, including 1,608 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 0.059 (1608 hom., cov: 29)
• Consequence: HCN3 NM_020897.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.89

Genes affected

HCN3 (HGNC:19183): (hyperpolarization activated cyclic nucleotide gated potassium channel 3) This gene encodes a multi-pass membrane protein that functions as a voltage gated cation channel. The encoded protein is a member of a family of closely related cyclic adenosine monophosphate-binding channel proteins. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HCN3	NM_020897.3	c.709-270G>A		intron_variant		ENST00000368358.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HCN3	ENST00000368358.4	c.709-270G>A		intron_variant		1	NM_020897.3	P1
HCN3	ENST00000467204.1	n.304-835G>A		intron_variant, non_coding_transcript_variant		5
HCN3	ENST00000496230.5	n.601-270G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0592 AC: 8995 AN: 151904 Hom.: 1601 Cov.: 29

Gnomad AFR AF: 0.00907

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.0384

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.0624

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0135

Gnomad OTH AF: 0.0570

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

GnomAD4 genome AF: 0.0592 AC: 9002 AN: 152022 Hom.: 1608 Cov.: 29 AF XY: 0.0683 AC XY: 5075 AN XY: 74292

Gnomad4 AFR AF: 0.00907

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.0384

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.0624

Gnomad4 NFE AF: 0.0135

Gnomad4 OTH AF: 0.0540

Alfa AF: 0.0504 Hom.: 316

Bravo AF: 0.0697

Asia WGS AF: 0.386 AC: 1337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	15
DANN	Benign	0.78

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: rs11264351; hg19: chr1-155253495;