20-49372912-T-G

Variant names:

• chr20-49372912-T-G
• rs147708122
• NM_004975.4:c.*71A>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_004975.4(KCNB1):​c.*71A>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 0.000584 in 1,309,734 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0029 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00028 (2 hom.)
• Consequence: KCNB1 NM_004975.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0530
• Publications: 1 publications found

Genes affected

KCNB1 (HGNC:6231): (potassium voltage-gated channel subfamily B member 1) Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shab-related subfamily. This member is a delayed rectifier potassium channel and its activity is modulated by some other family members. [provided by RefSeq, Jul 2008]

KCNB1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• developmental and epileptic encephalopathy, 26

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000290421 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 20-49372912-T-G is Benign according to our data. Variant chr20-49372912-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1214697.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 440 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNB1	NM_004975.4	c.*71A>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000371741.6	NP_004966.1
KCNB1	XM_011528799.3	c.*71A>C		3_prime_UTR_variant	Exon 3 of 3		XP_011527101.1
LOC105372649	XR_001754659.2	n.1201+40888T>G		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNB1	ENST00000371741.6	c.*71A>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_004975.4	ENSP00000360806.3

Frequencies

GnomAD3 genomes AF: 0.00289 AC: 440 AN: 152126 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000721

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.000281 AC: 325 AN: 1157490 Hom.: 2 Cov.: 16 AF XY: 0.000238 AC XY: 136 AN XY: 571928

African (AFR) AF: 0.0109 AC: 279 AN: 25646

American (AMR) AF: 0.000610 AC: 13 AN: 21298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18318

East Asian (EAS) AF: 0.00 AC: 0 AN: 35176

South Asian (SAS) AF: 0.00 AC: 0 AN: 61534

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45872

Middle Eastern (MID) AF: 0.000591 AC: 2 AN: 3386

European-Non Finnish (NFE) AF: 0.00000557 AC: 5 AN: 897046

Other (OTH) AF: 0.000528 AC: 26 AN: 49214

GnomAD4 genome AF: 0.00289 AC: 440 AN: 152244 Hom.: 3 Cov.: 32 AF XY: 0.00304 AC XY: 226 AN XY: 74434

African (AFR) AF: 0.0102 AC: 423 AN: 41546

American (AMR) AF: 0.000720 AC: 11 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

Alfa AF: 0.000471 Hom.: 0

Bravo AF: 0.00325

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 29, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.5
DANN	Benign	0.71
PhyloP100		-0.053
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

Other links and lift over

dbSNP: rs147708122; hg19: chr20-47989449;