chr4-20830183-C-A

Variant names:

• chr4-20830183-C-A
• rs9799795
• NM_025221.6:c.288+20360G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025221.6(KCNIP4):​c.288+20360G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 152,032 control chromosomes in the GnomAD database, including 12,149 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.39 (12149 hom., cov: 32)
• Consequence: KCNIP4 NM_025221.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025221.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNIP4	NM_025221.6	MANE Select	c.288+20360G>T		intron	N/A	NP_079497.2
	KCNIP4	NM_001363504.2		c.237+20360G>T		intron	N/A	NP_001350433.1	Q3YAB7
	KCNIP4	NM_147183.3		c.225+20360G>T		intron	N/A	NP_671712.1	Q6PIL6-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNIP4	ENST00000382152.7	TSL:5 MANE Select	c.288+20360G>T		intron	N/A	ENSP00000371587.2	Q6PIL6-1
	KCNIP4	ENST00000382149.9	TSL:1	c.237+20360G>T		intron	N/A	ENSP00000494651.1	Q3YAB7
	KCNIP4	ENST00000382150.8	TSL:1	c.225+20360G>T		intron	N/A	ENSP00000371585.4	Q6PIL6-4

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59095 AN: 151914 Hom.: 12143 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.390

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.389 AC: 59129 AN: 152032 Hom.: 12149 Cov.: 32 AF XY: 0.389 AC XY: 28919 AN XY: 74350

African (AFR) AF: 0.278 AC: 11540 AN: 41462

American (AMR) AF: 0.433 AC: 6612 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1417 AN: 3466

East Asian (EAS) AF: 0.157 AC: 810 AN: 5168

South Asian (SAS) AF: 0.361 AC: 1742 AN: 4822

European-Finnish (FIN) AF: 0.463 AC: 4888 AN: 10564

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.453 AC: 30812 AN: 67960

Other (OTH) AF: 0.390 AC: 824 AN: 2114

Alfa AF: 0.423 Hom.: 3780

Bravo AF: 0.382

Asia WGS AF: 0.292 AC: 1012 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.3
DANN	Benign	0.74
PhyloP100		0.082
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9799795; hg19: chr4-20831806;