11-17735870-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001112741.2(KCNC1):c.-133C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0558 in 1,052,872 control chromosomes in the GnomAD database, including 1,840 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.040 (175 hom., cov: 31)
  • Exomes 𝑓: 0.058 (1665 hom.)
• Consequence: KCNC1 NM_001112741.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.253

Genes affected

KCNC1 (HGNC:6233): (potassium voltage-gated channel subfamily C member 1) This gene encodes a member of a family of integral membrane proteins that mediate the voltage-dependent potassium ion permeability of excitable membranes. Alternative splicing is thought to result in two transcript variants encoding isoforms that differ at their C-termini. These isoforms have had conflicting names in the literature: the longer isoform has been called both "b" and "alpha", while the shorter isoform has been called both "a" and "beta" (PMIDs 1432046, 12091563). [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-17735870-C-A is Benign according to our data. Variant chr11-17735870-C-A is described in ClinVar as [Benign]. Clinvar id is 1226407.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNC1	NM_001112741.2	c.-133C>A		5_prime_UTR_variant	1/4	ENST00000265969.8
KCNC1	XM_047426916.1	c.-133C>A		5_prime_UTR_variant	1/4
KCNC1	XR_930866.3	n.1090C>A		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNC1	ENST00000265969.8	c.-133C>A		5_prime_UTR_variant	1/4	5	NM_001112741.2	P1

Frequencies

GnomAD3 genomes AF: 0.0403 AC: 6114 AN: 151638 Hom.: 175 Cov.: 31

Gnomad AFR AF: 0.0107

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.0283

Gnomad ASJ AF: 0.0300

Gnomad EAS AF: 0.000393

Gnomad SAS AF: 0.0234

Gnomad FIN AF: 0.0679

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.0620

Gnomad OTH AF: 0.0383

GnomAD4 exome AF: 0.0584 AC: 52633 AN: 901128 Hom.: 1665 Cov.: 12 AF XY: 0.0576 AC XY: 25593 AN XY: 444044

Gnomad4 AFR exome AF: 0.00891

Gnomad4 AMR exome AF: 0.0220

Gnomad4 ASJ exome AF: 0.0300

Gnomad4 EAS exome AF: 0.0000371

Gnomad4 SAS exome AF: 0.0265

Gnomad4 FIN exome AF: 0.0650

Gnomad4 NFE exome AF: 0.0654

Gnomad4 OTH exome AF: 0.0484

GnomAD4 genome AF: 0.0403 AC: 6113 AN: 151744 Hom.: 175 Cov.: 31 AF XY: 0.0398 AC XY: 2952 AN XY: 74162

Gnomad4 AFR AF: 0.0107

Gnomad4 AMR AF: 0.0283

Gnomad4 ASJ AF: 0.0300

Gnomad4 EAS AF: 0.000591

Gnomad4 SAS AF: 0.0236

Gnomad4 FIN AF: 0.0679

Gnomad4 NFE AF: 0.0619

Gnomad4 OTH AF: 0.0374

Alfa AF: 0.0535 Hom.: 231

Bravo AF: 0.0360

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	11
Dann	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs36101996; hg19: chr11-17757417;