rs11264351

Variant names:

• chr1-155283704-G-A
• rs11264351
• NM_020897.3:c.709-270G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HCN3	NM_020897.3	c.709-270G>A		intron_variant	Intron 2 of 7	ENST00000368358.4	NP_065948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HCN3	ENST00000368358.4	c.709-270G>A		intron_variant	Intron 2 of 7	1	NM_020897.3	ENSP00000357342.3
HCN3	ENST00000467204.1	n.304-835G>A		intron_variant	Intron 1 of 4	5
HCN3	ENST00000496230.5	n.601-270G>A		intron_variant	Intron 2 of 7	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

African (AFR) AF: 0.00907 AC: 376 AN: 41464

American (AMR) AF: 0.146 AC: 2226 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0384 AC: 133 AN: 3464

East Asian (EAS) AF: 0.683 AC: 3526 AN: 5160

South Asian (SAS) AF: 0.212 AC: 1019 AN: 4804

European-Finnish (FIN) AF: 0.0624 AC: 658 AN: 10552

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0135 AC: 920 AN: 67994

Other (OTH) AF: 0.0540 AC: 114 AN: 2110

Alfa AF: 0.0418 Hom.: 1836

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
PhyloP100		2.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11264351; hg19: chr1-155253495;