Variant 4-20758897-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_025221.6(KCNIP4):c.289-7T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0023 in 1,611,364 control chromosomes in the GnomAD database, including 28 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 0.0041 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 24 hom. )

Consequence

KCNIP4
NM_025221.6 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00009939

Clinical Significance

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

Conservation

PhyloP100: 1.72

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:):

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=-0.37).

BP6

Variant 4-20758897-A-G is Benign according to our data. Variant chr4-20758897-A-G is described in ClinVar as [Benign]. Clinvar id is 784037.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 625 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNIP4	NM_025221.6 linkuse as main transcript	c.289-7T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		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.289-7T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_025221.6	ENSP00000371587		Q6PIL6-1

Frequencies

GnomAD3 genomes

AF:

0.00411

AC:

626

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00690

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00726

Gnomad ASJ

AF:

0.0225

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00169

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00315

AC:

782

AN:

248010

Hom.:

AF XY:

0.00294

AC XY:

394

AN XY:

133918

show subpopulations

Gnomad AFR exome

AF:

0.00710

Gnomad AMR exome

AF:

0.00332

Gnomad ASJ exome

AF:

0.0202

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00312

Gnomad FIN exome

AF:

0.0000927

Gnomad NFE exome

AF:

0.00197

Gnomad OTH exome

AF:

0.00648

GnomAD4 exome

AF:

0.00212

AC:

3087

AN:

1459048

Hom.:

Cov.:

AF XY:

0.00213

AC XY:

1547

AN XY:

725786

show subpopulations

Gnomad4 AFR exome

AF:

0.00710

Gnomad4 AMR exome

AF:

0.00340

Gnomad4 ASJ exome

AF:

0.0187

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00267

Gnomad4 FIN exome

AF:

0.0000750

Gnomad4 NFE exome

AF:

0.00143

Gnomad4 OTH exome

AF:

0.00504

GnomAD4 genome

AF:

0.00410

AC:

625

AN:

152316

Hom.:

Cov.:

AF XY:

0.00428

AC XY:

319

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00688

Gnomad4 AMR

AF:

0.00725

Gnomad4 ASJ

AF:

0.0225

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00169

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00421

Hom.:

Bravo

AF:

0.00471

Asia WGS

AF:

0.00174

AC:

AN:

3468

EpiCase

AF:

0.00362

EpiControl

AF:

0.00351

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	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000099

dbscSNV1_RF

Benign

0.0020

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