chr2-10913614-C-T

Variant names:

• chr2-10913614-C-T
• rs3732105
• NM_002236.5:c.1188C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_002236.5(KCNF1):​c.1188C>T​(p.Ile396Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 1,612,932 control chromosomes in the GnomAD database, including 314,460 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (23870 hom., cov: 32)
  • Exomes 𝑓: 0.63 (290590 hom.)
• Consequence: KCNF1 NM_002236.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.204
• Publications: 20 publications found

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]

ENSG00000296957 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 2-10913614-C-T is Benign according to our data. Variant chr2-10913614-C-T is described in ClinVar as Benign. ClinVar VariationId is 1294515.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.204 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002236.5. 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
	KCNF1	NM_002236.5	MANE Select	c.1188C>T	p.Ile396Ile	synonymous	Exon 1 of 1	NP_002227.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNF1	ENST00000295082.3	TSL:6 MANE Select	c.1188C>T	p.Ile396Ile	synonymous	Exon 1 of 1	ENSP00000295082.1	Q9H3M0
	KCNF1	ENST00000961110.1		c.1188C>T	p.Ile396Ile	synonymous	Exon 2 of 2	ENSP00000631169.1
	ENSG00000296957	ENST00000743884.1		n.53+785G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83111 AN: 151942 Hom.: 23874 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.571

GnomAD2 exomes AF: 0.576 AC: 144441 AN: 250586 AF XY: 0.585

Gnomad AFR exome AF: 0.360

Gnomad AMR exome AF: 0.457

Gnomad ASJ exome AF: 0.651

Gnomad EAS exome AF: 0.533

Gnomad FIN exome AF: 0.584

Gnomad NFE exome AF: 0.652

Gnomad OTH exome AF: 0.587

GnomAD4 exome AF: 0.627 AC: 915387 AN: 1460872 Hom.: 290590 Cov.: 62 AF XY: 0.625 AC XY: 454569 AN XY: 726830

African (AFR) AF: 0.355 AC: 11892 AN: 33478

American (AMR) AF: 0.467 AC: 20901 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 16905 AN: 26134

East Asian (EAS) AF: 0.494 AC: 19599 AN: 39694

South Asian (SAS) AF: 0.540 AC: 46615 AN: 86248

European-Finnish (FIN) AF: 0.591 AC: 31031 AN: 52536

Middle Eastern (MID) AF: 0.567 AC: 3273 AN: 5768

European-Non Finnish (NFE) AF: 0.655 AC: 728417 AN: 1111920

Other (OTH) AF: 0.609 AC: 36754 AN: 60380

GnomAD4 genome AF: 0.547 AC: 83118 AN: 152060 Hom.: 23870 Cov.: 32 AF XY: 0.541 AC XY: 40220 AN XY: 74330

African (AFR) AF: 0.371 AC: 15381 AN: 41486

American (AMR) AF: 0.536 AC: 8189 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2229 AN: 3472

East Asian (EAS) AF: 0.510 AC: 2626 AN: 5148

South Asian (SAS) AF: 0.528 AC: 2537 AN: 4802

European-Finnish (FIN) AF: 0.574 AC: 6068 AN: 10574

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.648 AC: 44022 AN: 67968

Other (OTH) AF: 0.565 AC: 1195 AN: 2116

Alfa AF: 0.605 Hom.: 37411

Bravo AF: 0.536

Asia WGS AF: 0.478 AC: 1662 AN: 3478

EpiCase AF: 0.647

EpiControl AF: 0.655

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	2.0
DANN	Benign	0.84
PhyloP100		-0.20
Mutation Taster		=92/8	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: rs3732105; hg19: chr2-11053740; COSMIC: COSV54462394;