rs16902086

Variant names:

• chr5-45285650-A-G
• rs16902086
• NM_021072.4:c.1618+17949T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-45285650-A-G
• chr5-45285650-A-T

Variant summary

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

The NM_021072.4(HCN1):​c.1618+17949T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 151,784 control chromosomes in the GnomAD database, including 18,144 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 0.46 (18144 hom., cov: 32)
• Consequence: HCN1 NM_021072.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122
• Publications: 8 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HCN1	NM_021072.4	c.1618+17949T>C		intron_variant	Intron 6 of 7	ENST00000303230.6	NP_066550.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HCN1	ENST00000303230.6	c.1618+17949T>C		intron_variant	Intron 6 of 7	1	NM_021072.4	ENSP00000307342.4
HCN1	ENST00000673735.1	c.1618+17949T>C		intron_variant	Intron 6 of 8			ENSP00000501107.1
HCN1	ENST00000637305.1	n.781+17949T>C		intron_variant	Intron 5 of 6	5

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70435 AN: 151666 Hom.: 18094 Cov.: 32

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.465 AC: 70552 AN: 151784 Hom.: 18144 Cov.: 32 AF XY: 0.468 AC XY: 34692 AN XY: 74180

African (AFR) AF: 0.698 AC: 28901 AN: 41394

American (AMR) AF: 0.444 AC: 6735 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1564 AN: 3468

East Asian (EAS) AF: 0.470 AC: 2423 AN: 5150

South Asian (SAS) AF: 0.478 AC: 2306 AN: 4820

European-Finnish (FIN) AF: 0.344 AC: 3637 AN: 10576

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23634 AN: 67872

Other (OTH) AF: 0.439 AC: 927 AN: 2112

Alfa AF: 0.394 Hom.: 35653

Bravo AF: 0.482

Asia WGS AF: 0.521 AC: 1809 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.86
DANN	Benign	0.67
PhyloP100		-0.12
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: rs16902086; hg19: chr5-45285752;