rs747975797

chr5-45695870-TCGCCGCCGCCGCCGCCGC-Tchr5-45695870-TCGCCGCCGCCGCCGCCGC-TCGCchr5-45695870-TCGCCGCCGCCGCCGCCGC-TCGCCGCchr5-45695870-TCGCCGCCGCCGCCGCCGC-TCGCCGCCGCchr5-45695870-TCGCCGCCGCCGCCGCCGC-TCGCCGCCGCCGCchr5-45695870-TCGCCGCCGCCGCCGCCGC-TCGCCGCCGCCGCCGCchr5-45695870-TCGCCGCCGCCGCCGCCGC-TCGCCGCCGCCGCCGCCGCCGCchr5-45695870-TCGCCGCCGCCGCCGCCGC-TCGCCGCCGCCGCCGCCGCCGCCGCchr5-45695870-TCGCCGCCGCCGCCGCCGC-TCGCCGCCGCCGCCGCCGCCGCCGCCGCchr5-45695870-TCGCCGCCGCCGCCGCCGC-TCGCCGCCGCCGCCGCCGCCGCCGCCGCCGC

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_021072.4(HCN1):c.206_223del(p.Gly69_Gly74del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00000128 in 1,563,354 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: HCN1 NM_021072.4 inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.52

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_021072.4.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HCN1	NM_021072.4	c.206_223del	p.Gly69_Gly74del	inframe_deletion	1/8	ENST00000303230.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HCN1	ENST00000303230.6	c.206_223del	p.Gly69_Gly74del	inframe_deletion	1/8	1	NM_021072.4	P2
HCN1	ENST00000634658.1	c.206_223del	p.Gly69_Gly74del	inframe_deletion	1/2	3
HCN1	ENST00000673735.1	c.206_223del	p.Gly69_Gly74del	inframe_deletion	1/9			A2

Frequencies

GnomAD3 genomes AF: 0.00000676 AC: 1 AN: 147994 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000292

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.07e-7 AC: 1 AN: 1415360 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 702546

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000264

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000676 AC: 1 AN: 147994 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 1 AN XY: 72228

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000292

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs747975797; hg19: chr5-45695972;