Variant 4-20749655-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_025221.6(KCNIP4):c.429+7T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,574,060 control chromosomes in the GnomAD database, including 76,158 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 (★).

Frequency

Genomes: 𝑓 0.33 ( 8852 hom., cov: 32)

Exomes 𝑓: 0.30 ( 67306 hom. )

Consequence

KCNIP4
NM_025221.6 splice_region, intron

Scores

Splicing: ADA: 0.00006905

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.40

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:

PACRGL (HGNC:28442): (parkin coregulated like)

PACRGL links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 4-20749655-A-G is Benign according to our data. Variant chr4-20749655-A-G is described in ClinVar as [Benign]. Clinvar id is 3058996.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNIP4	NM_025221.6 linkuse as main transcript	c.429+7T>C		splice_region_variant, intron_variant		ENST00000382152.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNIP4	ENST00000382152.7 linkuse as main transcript	c.429+7T>C		splice_region_variant, intron_variant		5	NM_025221.6		Q6PIL6-1

Frequencies

GnomAD3 genomes

AF:

0.332

AC:

50506

AN:

151920

Hom.:

8851

Cov.:

show subpopulations

Gnomad AFR

AF:

0.440

Gnomad AMI

AF:

0.347

Gnomad AMR

AF:

0.263

Gnomad ASJ

AF:

0.329

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.363

Gnomad FIN

AF:

0.247

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.308

Gnomad OTH

AF:

0.336

GnomAD3 exomes

AF:

0.292

AC:

72185

AN:

247212

Hom.:

11443

AF XY:

0.298

AC XY:

39789

AN XY:

133630

show subpopulations

Gnomad AFR exome

AF:

0.435

Gnomad AMR exome

AF:

0.179

Gnomad ASJ exome

AF:

0.322

Gnomad EAS exome

AF:

0.164

Gnomad SAS exome

AF:

0.357

Gnomad FIN exome

AF:

0.234

Gnomad NFE exome

AF:

0.316

Gnomad OTH exome

AF:

0.306

GnomAD4 exome

AF:

0.302

AC:

429575

AN:

1422022

Hom.:

67306

Cov.:

AF XY:

0.304

AC XY:

215804

AN XY:

709022

show subpopulations

Gnomad4 AFR exome

AF:

0.437

Gnomad4 AMR exome

AF:

0.188

Gnomad4 ASJ exome

AF:

0.320

Gnomad4 EAS exome

AF:

0.137

Gnomad4 SAS exome

AF:

0.354

Gnomad4 FIN exome

AF:

0.241

Gnomad4 NFE exome

AF:

0.306

Gnomad4 OTH exome

AF:

0.314

GnomAD4 genome

AF:

0.332

AC:

50525

AN:

152038

Hom.:

8852

Cov.:

AF XY:

0.328

AC XY:

24342

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.439

Gnomad4 AMR

AF:

0.262

Gnomad4 ASJ

AF:

0.329

Gnomad4 EAS

AF:

0.146

Gnomad4 SAS

AF:

0.362

Gnomad4 FIN

AF:

0.247

Gnomad4 NFE

AF:

0.308

Gnomad4 OTH

AF:

0.335

Alfa

AF:

0.319

Hom.:

10573

Bravo

AF:

0.336

Asia WGS

AF:

0.280

AC:

977

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

KCNIP4-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 16, 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

-0.91

CADD

Benign

0.62

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000069

dbscSNV1_RF

Benign

0.0

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