7-66629021-C-T

Variant names:

• chr7-66629021-C-T
• rs35526611
• ENST00000503687.2:n.-44C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000503687.2(ENSG00000284461):​n.-44C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 1,475,286 control chromosomes in the GnomAD database, including 165,115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (20334 hom., cov: 31)
  • Exomes 𝑓: 0.46 (144781 hom.)
• Consequence: ENSG00000284461 ENST00000503687.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.106
• Publications: 13 publications found

Genes affected

ENSG00000284461 (HGNC:):

KCTD7 (HGNC:21957): (potassium channel tetramerization domain containing 7) This gene encodes a member of the potassium channel tetramerization domain-containing protein family. Family members are identified on a structural basis and contain an amino-terminal domain similar to the T1 domain present in the voltage-gated potassium channel. Mutations in this gene have been associated with progressive myoclonic epilepsy-3. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jan 2011]

KCTD7 Gene-Disease associations (from GenCC):

• progressive myoclonic epilepsy type 3

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet
• progressive myoclonus epilepsy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 7-66629021-C-T is Benign according to our data. Variant chr7-66629021-C-T is described in ClinVar as [Benign]. Clinvar id is 360584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCTD7	NM_153033.5	c.-44C>T		5_prime_UTR_variant	Exon 1 of 4	ENST00000639828.2	NP_694578.1
KCTD7	NM_001167961.2	c.-44C>T		5_prime_UTR_variant	Exon 1 of 5		NP_001161433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000284461	ENST00000503687.2	n.-44C>T		non_coding_transcript_exon_variant	Exon 1 of 13	2		ENSP00000421074.1
KCTD7	ENST00000639828.2	c.-44C>T		5_prime_UTR_variant	Exon 1 of 4	2	NM_153033.5	ENSP00000492240.1
ENSG00000284461	ENST00000503687.2	n.-44C>T		5_prime_UTR_variant	Exon 1 of 13	2		ENSP00000421074.1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76568 AN: 151462 Hom.: 20306 Cov.: 31

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.482

GnomAD2 exomes AF: 0.429 AC: 40765 AN: 94916 AF XY: 0.424

Gnomad AFR exome AF: 0.690

Gnomad AMR exome AF: 0.456

Gnomad ASJ exome AF: 0.361

Gnomad EAS exome AF: 0.284

Gnomad FIN exome AF: 0.384

Gnomad NFE exome AF: 0.477

Gnomad OTH exome AF: 0.445

GnomAD4 exome AF: 0.462 AC: 612215 AN: 1323718 Hom.: 144781 Cov.: 32 AF XY: 0.458 AC XY: 299366 AN XY: 652930

African (AFR) AF: 0.671 AC: 17969 AN: 26762

American (AMR) AF: 0.469 AC: 12926 AN: 27550

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 8426 AN: 22730

East Asian (EAS) AF: 0.194 AC: 5386 AN: 27828

South Asian (SAS) AF: 0.382 AC: 27911 AN: 73046

European-Finnish (FIN) AF: 0.390 AC: 17660 AN: 45262

Middle Eastern (MID) AF: 0.393 AC: 1803 AN: 4588

European-Non Finnish (NFE) AF: 0.475 AC: 495429 AN: 1041918

Other (OTH) AF: 0.457 AC: 24705 AN: 54034

GnomAD4 genome AF: 0.506 AC: 76639 AN: 151568 Hom.: 20334 Cov.: 31 AF XY: 0.499 AC XY: 36984 AN XY: 74072

African (AFR) AF: 0.659 AC: 27294 AN: 41404

American (AMR) AF: 0.484 AC: 7386 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1309 AN: 3466

East Asian (EAS) AF: 0.256 AC: 1316 AN: 5132

South Asian (SAS) AF: 0.361 AC: 1738 AN: 4818

European-Finnish (FIN) AF: 0.397 AC: 4151 AN: 10454

Middle Eastern (MID) AF: 0.342 AC: 100 AN: 292

European-Non Finnish (NFE) AF: 0.472 AC: 32002 AN: 67752

Other (OTH) AF: 0.479 AC: 1006 AN: 2100

Alfa AF: 0.489 Hom.: 2292

Bravo AF: 0.518

Asia WGS AF: 0.317 AC: 1078 AN: 3398

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 68% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 63. Only high quality variants are reported. -

Progressive myoclonic epilepsy type 3 Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	14
DANN	Benign	0.87
PhyloP100		0.11
PromoterAI		0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Mutation Taster		=148/152	disease causing

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: rs35526611; hg19: chr7-66094008; COSMIC: COSV107297323; COSMIC: COSV107297323;