Variant chr2-10912894-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002236.5(KCNF1):c.468A>G(p.Ala156=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.842 in 1,611,932 control chromosomes in the GnomAD database, including 573,300 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.87 ( 57557 hom., cov: 36)

Exomes 𝑓: 0.84 ( 515743 hom. )

Consequence

KCNF1
NM_002236.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0280

Variant links:

Genes affected

KCNF1 (HGNC:6246): (potassium voltage-gated channel modifier subfamily F member 1) 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 F. This gene is intronless and expressed in all tissues tested, including the heart, skeletal muscle, brain, kidney, and pancreas. [provided by RefSeq, Jul 2008]

KCNF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 2-10912894-A-G is Benign according to our data. Variant chr2-10912894-A-G is described in ClinVar as [Benign]. Clinvar id is 1288667.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.028 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNF1	NM_002236.5 linkuse as main transcript	c.468A>G	p.Ala156=	synonymous_variant	1/1	ENST00000295082.3	NP_002227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNF1	ENST00000295082.3 linkuse as main transcript	c.468A>G	p.Ala156=	synonymous_variant	1/1		NM_002236.5	ENSP00000295082	P1

Frequencies

GnomAD3 genomes

AF:

0.867

AC:

131933

AN:

152152

Hom.:

57511

Cov.:

show subpopulations

Gnomad AFR

AF:

0.954

Gnomad AMI

AF:

0.887

Gnomad AMR

AF:

0.843

Gnomad ASJ

AF:

0.853

Gnomad EAS

AF:

0.955

Gnomad SAS

AF:

0.817

Gnomad FIN

AF:

0.768

Gnomad MID

AF:

0.911

Gnomad NFE

AF:

0.832

Gnomad OTH

AF:

0.868

GnomAD3 exomes

AF:

0.853

AC:

208956

AN:

245108

Hom.:

89381

AF XY:

0.848

AC XY:

113265

AN XY:

133578

show subpopulations

Gnomad AFR exome

AF:

0.954

Gnomad AMR exome

AF:

0.872

Gnomad ASJ exome

AF:

0.862

Gnomad EAS exome

AF:

0.955

Gnomad SAS exome

AF:

0.820

Gnomad FIN exome

AF:

0.779

Gnomad NFE exome

AF:

0.838

Gnomad OTH exome

AF:

0.842

GnomAD4 exome

AF:

0.840

AC:

1225592

AN:

1459662

Hom.:

515743

Cov.:

AF XY:

0.838

AC XY:

608823

AN XY:

726240

show subpopulations

Gnomad4 AFR exome

AF:

0.955

Gnomad4 AMR exome

AF:

0.868

Gnomad4 ASJ exome

AF:

0.859

Gnomad4 EAS exome

AF:

0.959

Gnomad4 SAS exome

AF:

0.822

Gnomad4 FIN exome

AF:

0.780

Gnomad4 NFE exome

AF:

0.833

Gnomad4 OTH exome

AF:

0.855

GnomAD4 genome

AF:

0.867

AC:

132034

AN:

152270

Hom.:

57557

Cov.:

AF XY:

0.862

AC XY:

64177

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.954

Gnomad4 AMR

AF:

0.843

Gnomad4 ASJ

AF:

0.853

Gnomad4 EAS

AF:

0.956

Gnomad4 SAS

AF:

0.816

Gnomad4 FIN

AF:

0.768

Gnomad4 NFE

AF:

0.832

Gnomad4 OTH

AF:

0.866

Alfa

AF:

0.842

Hom.:

20370

Bravo

AF:

0.879

Asia WGS

AF:

0.884

AC:

3073

AN:

3476

EpiCase

AF:

0.843

EpiControl

AF:

0.852

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	GeneDx	Jun 18, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

9.7

DANN

Benign

0.73

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