Variant chr17-42160331-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_012285.3(KCNH4):c.2763C>T(p.Ser921Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00582 in 1,614,106 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0059 ( 28 hom. )

Consequence

KCNH4
NM_012285.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.00

Variant links:

Genes affected

KCNH4 (HGNC:6253): (potassium voltage-gated channel subfamily H member 4) 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. The gene is brain-specific, and located in the neocortex and the striatum. It may be involved in cellular excitability of restricted neurons in the central nervous system. [provided by RefSeq, Jul 2008]

KCNH4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 17-42160331-G-A is Benign according to our data. Variant chr17-42160331-G-A is described in ClinVar as [Benign]. Clinvar id is 771027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4 with no splicing effect.

BS2

High AC in GnomAd4 at 695 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNH4	NM_012285.3 linkuse as main transcript	c.2763C>T	p.Ser921Ser	synonymous_variant	16/17	ENST00000264661.4	NP_036417.1	Q9UQ05

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNH4	ENST00000264661.4 linkuse as main transcript	c.2763C>T	p.Ser921Ser	synonymous_variant	16/17	1	NM_012285.3	ENSP00000264661.2		Q9UQ05
KCNH4	ENST00000607371.5 linkuse as main transcript	c.2763C>T	p.Ser921Ser	synonymous_variant	16/17	5		ENSP00000475564.1		Q9UQ05

Frequencies

GnomAD3 genomes

AF:

0.00457

AC:

695

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.00353

Gnomad FIN

AF:

0.0113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00665

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00442

AC:

1110

AN:

251272

Hom.:

AF XY:

0.00445

AC XY:

605

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.00268

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00336

Gnomad FIN exome

AF:

0.00730

Gnomad NFE exome

AF:

0.00635

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00595

AC:

8697

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00595

AC XY:

4326

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.00181

Gnomad4 ASJ exome

AF:

0.00222

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00401

Gnomad4 FIN exome

AF:

0.00715

Gnomad4 NFE exome

AF:

0.00676

Gnomad4 OTH exome

AF:

0.00449

GnomAD4 genome

AF:

0.00457

AC:

695

AN:

152228

Hom.:

Cov.:

AF XY:

0.00470

AC XY:

350

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00149

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000581

Gnomad4 SAS

AF:

0.00353

Gnomad4 FIN

AF:

0.0113

Gnomad4 NFE

AF:

0.00665

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00589

Hom.:

Bravo

AF:

0.00356

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.00573

EpiControl

AF:

0.00652

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.22

DANN

Benign

0.30

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over