chr5-45266487-A-G

Position:

• chr5-45266487-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021072.4(HCN1):​c.1783+602T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,054 control chromosomes in the GnomAD database, including 11,141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.34 (11141 hom., cov: 32)
• Consequence: HCN1 NM_021072.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.750

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 5-45266487-A-G is Benign according to our data. Variant chr5-45266487-A-G is described in ClinVar as [Benign]. Clinvar id is 3256856.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HCN1	NM_021072.4	c.1783+602T>C		intron_variant		ENST00000303230.6	NP_066550.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HCN1	ENST00000303230.6	c.1783+602T>C		intron_variant		1	NM_021072.4	ENSP00000307342.4
HCN1	ENST00000673735.1	c.*8+28T>C		intron_variant				ENSP00000501107.1
HCN1	ENST00000637305.1	n.946+602T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51986 AN: 151936 Hom.: 11142 Cov.: 32

Gnomad AFR AF: 0.0839

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.342 AC: 51986 AN: 152054 Hom.: 11141 Cov.: 32 AF XY: 0.342 AC XY: 25438 AN XY: 74302

Gnomad4 AFR AF: 0.0836

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.403

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.379

Alfa AF: 0.430 Hom.: 20684

Bravo AF: 0.326

Asia WGS AF: 0.250 AC: 871 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 31, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 73% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 68. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.6
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: rs4866929; hg19: chr5-45266589;