ENST00000379472.4:c.*1934A>C

Variant names:

• chr11-17774564-A-C
• rs60349741
• ENST00000379472.4:c.*1934A>C

Variant summary

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

The ENST00000379472.4(KCNC1):​c.*1934A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00501 in 985,572 control chromosomes in the GnomAD database, including 136 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 0.019 (99 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (37 hom.)
• Consequence: KCNC1 ENST00000379472.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124
• Publications: 11 publications found

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]

KCNC1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics, ClinGen
• progressive myoclonic epilepsy type 7

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• progressive myoclonus epilepsy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0585 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000379472.4. 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
	KCNC1	NM_001112741.2	MANE Select	c.1504+1966A>C		intron	N/A	NP_001106212.1	P48547-2
	KCNC1	NM_004976.4		c.*1934A>C		3_prime_UTR	Exon 2 of 2	NP_004967.1	P48547-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNC1	ENST00000379472.4	TSL:1	c.*1934A>C		3_prime_UTR	Exon 2 of 2	ENSP00000368785.3	P48547-1
	KCNC1	ENST00000265969.8	TSL:5 MANE Select	c.1504+1966A>C		intron	N/A	ENSP00000265969.7	P48547-2
	KCNC1	ENST00000639325.2	TSL:5	c.1504+1966A>C		intron	N/A	ENSP00000492663.2	A0A1W2PNZ3

Frequencies

GnomAD3 genomes AF: 0.0191 AC: 2899 AN: 152156 Hom.: 98 Cov.: 32

Gnomad AFR AF: 0.0604

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00118

Gnomad OTH AF: 0.0163

GnomAD4 exome AF: 0.00243 AC: 2028 AN: 833298 Hom.: 37 Cov.: 36 AF XY: 0.00237 AC XY: 913 AN XY: 384842

African (AFR) AF: 0.0586 AC: 925 AN: 15794

American (AMR) AF: 0.00711 AC: 7 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.0215 AC: 111 AN: 5152

East Asian (EAS) AF: 0.00 AC: 0 AN: 3630

South Asian (SAS) AF: 0.000182 AC: 3 AN: 16464

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 290

Middle Eastern (MID) AF: 0.0130 AC: 21 AN: 1620

European-Non Finnish (NFE) AF: 0.00104 AC: 790 AN: 762056

Other (OTH) AF: 0.00626 AC: 171 AN: 27308

GnomAD4 genome AF: 0.0191 AC: 2907 AN: 152274 Hom.: 99 Cov.: 32 AF XY: 0.0188 AC XY: 1396 AN XY: 74450

African (AFR) AF: 0.0605 AC: 2511 AN: 41538

American (AMR) AF: 0.0141 AC: 216 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0170 AC: 59 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00118 AC: 80 AN: 68016

Other (OTH) AF: 0.0161 AC: 34 AN: 2114

Alfa AF: 0.0202 Hom.: 31

Bravo AF: 0.0218

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.52
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs60349741;

hg19: chr11-17796111;