Genetic Variant NM_033272.4:c.1954+91G>A (chr2-162435107-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0870

Publications

10 publications found

Variant links:

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

KCNH7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNH7	NM_033272.4 link	c.1954+91G>A		intron_variant	Intron 8 of 15	ENST00000332142.10	NP_150375.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNH7	ENST00000332142.10 link	c.1954+91G>A		intron_variant	Intron 8 of 15	1	NM_033272.4	ENSP00000331727.5
KCNH7	ENST00000328032.8 link	c.1933+91G>A		intron_variant	Intron 7 of 7	1		ENSP00000333781.4

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

22239

AN:

151818

Hom.:

4338

Cov.:

show subpopulations

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

show subpopulations

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:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

939

1878

2817

3756

4695

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

416

832

1248

1664

2080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.147

AC:

22336

AN:

151936

Hom.:

4374

Cov.:

AF XY:

0.144

AC XY:

10684

AN XY:

74268

show subpopulations

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:

AN:

4820

European-Finnish (FIN)

AF:

0.00160

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00297

AC:

202

AN:

67962

Other (OTH)

AF:

0.129

AC:

272

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

683

1366

2049

2732

3415

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

190

380

570

760

950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.69

PhyloP100

-0.087

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over