11-17736074-G-A

Variant names:

• chr11-17736074-G-A
• rs76929858
• NM_001112741.2:c.72G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001112741.2(KCNC1):​c.72G>A​(p.Ser24Ser) variant causes a synonymous change. The variant allele was found at a frequency of 0.00541 in 1,601,310 control chromosomes in the GnomAD database, including 408 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (215 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (193 hom.)
• Consequence: KCNC1 NM_001112741.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 3.90
• Publications: 1 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: ClinGen, Ambry Genetics
• progressive myoclonic epilepsy type 7

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

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 11-17736074-G-A is Benign according to our data. Variant chr11-17736074-G-A is described in ClinVar as Benign. ClinVar VariationId is 447617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0962 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001112741.2. 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.72G>A	p.Ser24Ser	synonymous	Exon 1 of 4	NP_001106212.1	P48547-2
	KCNC1	NM_004976.4		c.72G>A	p.Ser24Ser	synonymous	Exon 1 of 2	NP_004967.1	P48547-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNC1	ENST00000265969.8	TSL:5 MANE Select	c.72G>A	p.Ser24Ser	synonymous	Exon 1 of 4	ENSP00000265969.7	P48547-2
	KCNC1	ENST00000379472.4	TSL:1	c.72G>A	p.Ser24Ser	synonymous	Exon 1 of 2	ENSP00000368785.3	P48547-1
	KCNC1	ENST00000639325.2	TSL:5	c.72G>A	p.Ser24Ser	synonymous	Exon 1 of 5	ENSP00000492663.2	A0A1W2PNZ3

Frequencies

GnomAD3 genomes AF: 0.0286 AC: 4345 AN: 152158 Hom.: 216 Cov.: 32

Gnomad AFR AF: 0.0989

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.0201

GnomAD2 exomes AF: 0.00779 AC: 1799 AN: 230924 AF XY: 0.00559

Gnomad AFR exome AF: 0.108

Gnomad AMR exome AF: 0.00461

Gnomad ASJ exome AF: 0.00290

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000352

Gnomad OTH exome AF: 0.00298

GnomAD4 exome AF: 0.00298 AC: 4313 AN: 1449034 Hom.: 193 Cov.: 32 AF XY: 0.00252 AC XY: 1813 AN XY: 719758

African (AFR) AF: 0.103 AC: 3420 AN: 33150

American (AMR) AF: 0.00518 AC: 227 AN: 43814

Ashkenazi Jewish (ASJ) AF: 0.00277 AC: 71 AN: 25610

East Asian (EAS) AF: 0.00 AC: 0 AN: 39226

South Asian (SAS) AF: 0.000213 AC: 18 AN: 84516

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51062

Middle Eastern (MID) AF: 0.00488 AC: 28 AN: 5738

European-Non Finnish (NFE) AF: 0.000171 AC: 189 AN: 1106112

Other (OTH) AF: 0.00602 AC: 360 AN: 59806

GnomAD4 genome AF: 0.0286 AC: 4348 AN: 152276 Hom.: 215 Cov.: 32 AF XY: 0.0276 AC XY: 2056 AN XY: 74462

African (AFR) AF: 0.0987 AC: 4101 AN: 41560

American (AMR) AF: 0.0103 AC: 158 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00260 AC: 9 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.000500 AC: 34 AN: 68014

Other (OTH) AF: 0.0199 AC: 42 AN: 2114

Alfa AF: 0.00870 Hom.: 16

Bravo AF: 0.0326

Asia WGS AF: 0.00491 AC: 18 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Inborn genetic diseases (1)
-	-	1	not specified (1)
-	-	1	Progressive myoclonic epilepsy type 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	14
DANN	Uncertain	0.98
PhyloP100		3.9
Mutation Taster		=95/5	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: rs76929858; hg19: chr11-17757621;