rs17344896

Variant names:

• chr5-45614123-T-C
• rs17344896
• NM_021072.4:c.849+31062A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-45614123-T-C
• chr5-45614123-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021072.4(HCN1):​c.849+31062A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0719 in 152,246 control chromosomes in the GnomAD database, including 574 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 0.072 (574 hom., cov: 31)
• Consequence: HCN1 NM_021072.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 24

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• generalized epilepsy with febrile seizures plus

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• generalized epilepsy with febrile seizures plus, type 10

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HCN1	NM_021072.4	c.849+31062A>G		intron_variant	Intron 2 of 7	ENST00000303230.6	NP_066550.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HCN1	ENST00000303230.6	c.849+31062A>G		intron_variant	Intron 2 of 7	1	NM_021072.4	ENSP00000307342.4
HCN1	ENST00000673735.1	c.849+31062A>G		intron_variant	Intron 2 of 8			ENSP00000501107.1

Frequencies

GnomAD3 genomes AF: 0.0720 AC: 10949 AN: 152128 Hom.: 575 Cov.: 31

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0769

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0636

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.0983

Gnomad OTH AF: 0.0917

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

GnomAD4 genome AF: 0.0719 AC: 10939 AN: 152246 Hom.: 574 Cov.: 31 AF XY: 0.0716 AC XY: 5327 AN XY: 74448

African (AFR) AF: 0.0180 AC: 748 AN: 41568

American (AMR) AF: 0.0768 AC: 1172 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 801 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.117 AC: 566 AN: 4832

European-Finnish (FIN) AF: 0.0636 AC: 675 AN: 10618

Middle Eastern (MID) AF: 0.151 AC: 44 AN: 292

European-Non Finnish (NFE) AF: 0.0983 AC: 6682 AN: 67996

Other (OTH) AF: 0.0903 AC: 191 AN: 2116

Alfa AF: 0.0869 Hom.: 359

Bravo AF: 0.0695

Asia WGS AF: 0.0430 AC: 149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.69
PhyloP100		0.15
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: rs17344896; hg19: chr5-45614225;