20-63361854-C-T

Position:

• chr20-63361854-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NR_110634.1(LOC100130587):​n.219C>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 0.167 in 152,200 control chromosomes in the GnomAD database, including 2,603 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2602 hom., cov: 30)
  • Exomes 𝑓: 0.090 (1 hom.)
• Consequence: LOC100130587 NR_110634.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.193

Genes affected

(HGNC:):

CHRNA4 (HGNC:1958): (cholinergic receptor nicotinic alpha 4 subunit) This gene encodes a nicotinic acetylcholine receptor, which belongs to a superfamily of ligand-gated ion channels that play a role in fast signal transmission at synapses. These pentameric receptors can bind acetylcholine, which causes an extensive change in conformation that leads to the opening of an ion-conducting channel across the plasma membrane. This protein is an integral membrane receptor subunit that can interact with either nAChR beta-2 or nAChR beta-4 to form a functional receptor. Mutations in this gene cause nocturnal frontal lobe epilepsy type 1. Polymorphisms in this gene that provide protection against nicotine addiction have been described. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 20-63361854-C-T is Benign according to our data. Variant chr20-63361854-C-T is described in ClinVar as [Benign]. Clinvar id is 1169561.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC100130587	NR_110634.1	n.219C>T		non_coding_transcript_exon_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000370257.1	n.219C>T		non_coding_transcript_exon_variant	2/5	2
CHRNA4	ENST00000463705.5	n.1032-10827G>A		intron_variant, non_coding_transcript_variant		1
CHRNA4	ENST00000675470.1	c.-689G>A		5_prime_UTR_variant	3/5			ENSP00000502096

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25399 AN: 151982 Hom.: 2603 Cov.: 30

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.187

GnomAD4 exome AF: 0.0900 AC: 9 AN: 100 Hom.: 1 Cov.: 0 AF XY: 0.0811 AC XY: 6 AN XY: 74

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.667

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0429

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.167 AC: 25411 AN: 152100 Hom.: 2602 Cov.: 30 AF XY: 0.171 AC XY: 12688 AN XY: 74330

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.575

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.185

Alfa AF: 0.143 Hom.: 249

Bravo AF: 0.169

Asia WGS AF: 0.375 AC: 1301 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Autosomal dominant nocturnal frontal lobe epilepsy Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	10
DANN	Benign	0.91

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6122429; hg19: chr20-61993206;