rs60349741

Positions:

• chr11-17774564-A-C
• chr11-17774564-A-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNC1	NM_001112741.2	c.1504+1966A>C		intron_variant		ENST00000265969.8	NP_001106212.1
KCNC1	NM_004976.4	c.*1934A>C		3_prime_UTR_variant	2/2		NP_004967.1
KCNC1	XM_047426916.1	c.1566+734A>C		intron_variant			XP_047282872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNC1	ENST00000265969.8	c.1504+1966A>C		intron_variant		5	NM_001112741.2	ENSP00000265969	P1

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

Gnomad4 AFR exome AF: 0.0586

Gnomad4 AMR exome AF: 0.00711

Gnomad4 ASJ exome AF: 0.0215

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000182

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00104

Gnomad4 OTH exome AF: 0.00626

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

Gnomad4 AFR AF: 0.0605

Gnomad4 AMR AF: 0.0141

Gnomad4 ASJ AF: 0.0170

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00118

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.00267 Hom.: 1

Bravo AF: 0.0218

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.52

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: rs60349741; hg19: chr11-17796111;