rs12104705

Positions:

• chr2-162435107-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033272.4(KCNH7):​c.1954+91G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0393 in 1,222,190 control chromosomes in the GnomAD database, including 7,926 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 0.15 (4374 hom., cov: 32)
  • Exomes 𝑓: 0.024 (3552 hom.)
• Consequence: KCNH7 NM_033272.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870

Genes affected

KCNH7 (HGNC:18863): (potassium voltage-gated channel subfamily H member 7) Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium channel, voltage-gated, subfamily H. This member is a pore-forming (alpha) subunit. There are at least two alternatively spliced transcript variants derived from this gene and encoding distinct isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNH7	NM_033272.4	c.1954+91G>A		intron_variant		ENST00000332142.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNH7	ENST00000332142.10	c.1954+91G>A		intron_variant		1	NM_033272.4	P1
KCNH7	ENST00000328032.8	c.1933+91G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22239 AN: 151818 Hom.: 4338 Cov.: 32

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.0502

Gnomad EAS AF: 0.0897

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.00297

Gnomad OTH AF: 0.127

GnomAD4 exome AF: 0.0240 AC: 25689 AN: 1070254 Hom.: 3552 AF XY: 0.0218 AC XY: 11664 AN XY: 535450

Gnomad4 AFR exome AF: 0.450

Gnomad4 AMR exome AF: 0.224

Gnomad4 ASJ exome AF: 0.0573

Gnomad4 EAS exome AF: 0.105

Gnomad4 SAS exome AF: 0.00790

Gnomad4 FIN exome AF: 0.00166

Gnomad4 NFE exome AF: 0.00160

Gnomad4 OTH exome AF: 0.0508

GnomAD4 genome AF: 0.147 AC: 22336 AN: 151936 Hom.: 4374 Cov.: 32 AF XY: 0.144 AC XY: 10684 AN XY: 74268

Gnomad4 AFR AF: 0.437

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.0502

Gnomad4 EAS AF: 0.0893

Gnomad4 SAS AF: 0.0110

Gnomad4 FIN AF: 0.00160

Gnomad4 NFE AF: 0.00297

Gnomad4 OTH AF: 0.129

Alfa AF: 0.0438 Hom.: 169

Bravo AF: 0.180

Asia WGS AF: 0.0890 AC: 308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.5
DANN	Benign	0.69

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: rs12104705; hg19: chr2-163291617; COSMIC: COSV59790733;