Variant 4-20850543-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_025221.6(KCNIP4):c.288T>C(p.Asn96=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 1,610,388 control chromosomes in the GnomAD database, including 135,184 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.35 ( 10443 hom., cov: 33)

Exomes 𝑓: 0.41 ( 124741 hom. )

Consequence

KCNIP4
NM_025221.6 splice_region, synonymous

Scores

Splicing: ADA: 0.0002750

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.618

Variant links:

Genes affected

KCNIP4 (HGNC:30083): (potassium voltage-gated channel interacting protein 4) This gene encodes a member of the family of voltage-gated potassium (Kv) channel-interacting proteins (KCNIPs), which belong to the recoverin branch of the EF-hand superfamily. Members of the KCNIP family are small calcium binding proteins. They all have EF-hand-like domains, and differ from each other in the N-terminus. They are integral subunit components of native Kv4 channel complexes. They may regulate A-type currents, and hence neuronal excitability, in response to changes in intracellular calcium. This protein member also interacts with presenilin. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

KCNIP4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 4-20850543-A-G is Benign according to our data. Variant chr4-20850543-A-G is described in ClinVar as [Benign]. Clinvar id is 3060067.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.618 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNIP4	NM_025221.6 linkuse as main transcript	c.288T>C	p.Asn96=	splice_region_variant, synonymous_variant	3/9	ENST00000382152.7	NP_079497.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNIP4	ENST00000382152.7 linkuse as main transcript	c.288T>C	p.Asn96=	splice_region_variant, synonymous_variant	3/9	5	NM_025221.6	ENSP00000371587		Q6PIL6-1

Frequencies

GnomAD3 genomes

AF:

0.352

AC:

53548

AN:

151988

Hom.:

10433

Cov.:

show subpopulations

Gnomad AFR

AF:

0.174

Gnomad AMI

AF:

0.412

Gnomad AMR

AF:

0.455

Gnomad ASJ

AF:

0.420

Gnomad EAS

AF:

0.415

Gnomad SAS

AF:

0.408

Gnomad FIN

AF:

0.444

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.410

Gnomad OTH

AF:

0.374

GnomAD3 exomes

AF:

0.415

AC:

103943

AN:

250332

Hom.:

22516

AF XY:

0.416

AC XY:

56287

AN XY:

135300

show subpopulations

Gnomad AFR exome

AF:

0.168

Gnomad AMR exome

AF:

0.527

Gnomad ASJ exome

AF:

0.425

Gnomad EAS exome

AF:

0.417

Gnomad SAS exome

AF:

0.406

Gnomad FIN exome

AF:

0.439

Gnomad NFE exome

AF:

0.413

Gnomad OTH exome

AF:

0.421

GnomAD4 exome

AF:

0.410

AC:

597867

AN:

1458282

Hom.:

124741

Cov.:

AF XY:

0.411

AC XY:

297810

AN XY:

725440

show subpopulations

Gnomad4 AFR exome

AF:

0.161

Gnomad4 AMR exome

AF:

0.518

Gnomad4 ASJ exome

AF:

0.427

Gnomad4 EAS exome

AF:

0.399

Gnomad4 SAS exome

AF:

0.403

Gnomad4 FIN exome

AF:

0.439

Gnomad4 NFE exome

AF:

0.413

Gnomad4 OTH exome

AF:

0.402

GnomAD4 genome

AF:

0.352

AC:

53580

AN:

152106

Hom.:

10443

Cov.:

AF XY:

0.355

AC XY:

26419

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.174

Gnomad4 AMR

AF:

0.456

Gnomad4 ASJ

AF:

0.420

Gnomad4 EAS

AF:

0.415

Gnomad4 SAS

AF:

0.407

Gnomad4 FIN

AF:

0.444

Gnomad4 NFE

AF:

0.410

Gnomad4 OTH

AF:

0.377

Alfa

AF:

0.409

Hom.:

27293

Bravo

AF:

0.345

Asia WGS

AF:

0.448

AC:

1554

AN:

3478

EpiCase

AF:

0.411

EpiControl

AF:

0.412

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KCNIP4-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

4.2

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00027

dbscSNV1_RF

Benign

0.20

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