rs12104705

Variant names:

• chr2-162435107-C-T
• rs12104705
• NM_033272.4:c.1954+91G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

KCNH7 Gene-Disease associations (from GenCC):

• epilepsy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033272.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNH7	NM_033272.4	MANE Select	c.1954+91G>A		intron	N/A	NP_150375.2
	KCNH7	NM_173162.3		c.1933+91G>A		intron	N/A	NP_775185.1	Q9NS40-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNH7	ENST00000332142.10	TSL:1 MANE Select	c.1954+91G>A		intron	N/A	ENSP00000331727.5	Q9NS40-1
	KCNH7	ENST00000328032.8	TSL:1	c.1933+91G>A		intron	N/A	ENSP00000333781.4	Q9NS40-2

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

African (AFR) AF: 0.450 AC: 10603 AN: 23562

American (AMR) AF: 0.224 AC: 6002 AN: 26760

Ashkenazi Jewish (ASJ) AF: 0.0573 AC: 1037 AN: 18106

East Asian (EAS) AF: 0.105 AC: 3715 AN: 35536

South Asian (SAS) AF: 0.00790 AC: 473 AN: 59868

European-Finnish (FIN) AF: 0.00166 AC: 67 AN: 40274

Middle Eastern (MID) AF: 0.0277 AC: 132 AN: 4764

European-Non Finnish (NFE) AF: 0.00160 AC: 1301 AN: 814946

Other (OTH) AF: 0.0508 AC: 2359 AN: 46438

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

African (AFR) AF: 0.437 AC: 18066 AN: 41384

American (AMR) AF: 0.202 AC: 3073 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.0502 AC: 174 AN: 3468

East Asian (EAS) AF: 0.0893 AC: 461 AN: 5160

South Asian (SAS) AF: 0.0110 AC: 53 AN: 4820

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10608

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.00297 AC: 202 AN: 67962

Other (OTH) AF: 0.129 AC: 272 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.5
DANN	Benign	0.69
PhyloP100		-0.087
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: rs12104705; hg19: chr2-163291617; COSMIC: COSV59790733;