rs2072658

chr1-154567749-G-A

Variant summary

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

The ENST00000666466.2(ENSG00000286391):n.1C>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 0.0233 in 378,710 control chromosomes in the GnomAD database, including 522 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (144 hom., cov: 32)
  • Exomes 𝑓: 0.026 (378 hom.)
• Consequence: ENST00000666466.2 non_coding_transcript_exon
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.16

Genes affected

(HGNC:):

CHRNB2 (HGNC:1962): (cholinergic receptor nicotinic beta 2 subunit) Neuronal acetylcholine receptors are homo- or heteropentameric complexes composed of homologous alpha and beta subunits. They belong to a superfamily of ligand-gated ion channels which allow the flow of sodium and potassium across the plasma membrane in response to ligands such as acetylcholine and nicotine. This gene encodes one of several beta subunits. Mutations in this gene are associated with autosomal dominant nocturnal frontal lobe epilepsy. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 1-154567749-G-A is Benign according to our data. Variant chr1-154567749-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 673243.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNB2	NM_000748.3			upstream_gene_variant		ENST00000368476.4
LOC107985206	XR_001738238.3			upstream_gene_variant
CHRNB2	XR_001736952.3			upstream_gene_variant
LOC107985206	XR_001738237.2			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000666466.2	n.1C>T		non_coding_transcript_exon_variant	1/2
CHRNB2	ENST00000368476.4			upstream_gene_variant		1	NM_000748.3	P4

Frequencies

GnomAD3 genomes AF: 0.0195 AC: 2957 AN: 151630 Hom.: 141 Cov.: 32

Gnomad AFR AF: 0.00389

Gnomad AMI AF: 0.00769

Gnomad AMR AF: 0.0686

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.00685

Gnomad FIN AF: 0.00190

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0117

Gnomad OTH AF: 0.0140

GnomAD4 exome AF: 0.0257 AC: 5839 AN: 226970 Hom.: 378 Cov.: 0 AF XY: 0.0243 AC XY: 2820 AN XY: 115866

Gnomad4 AFR exome AF: 0.00238

Gnomad4 AMR exome AF: 0.0859

Gnomad4 ASJ exome AF: 0.000921

Gnomad4 EAS exome AF: 0.197

Gnomad4 SAS exome AF: 0.00416

Gnomad4 FIN exome AF: 0.00268

Gnomad4 NFE exome AF: 0.0112

Gnomad4 OTH exome AF: 0.0215

GnomAD4 genome AF: 0.0196 AC: 2967 AN: 151740 Hom.: 144 Cov.: 32 AF XY: 0.0208 AC XY: 1545 AN XY: 74154

Gnomad4 AFR AF: 0.00388

Gnomad4 AMR AF: 0.0691

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.00706

Gnomad4 FIN AF: 0.00190

Gnomad4 NFE AF: 0.0117

Gnomad4 OTH AF: 0.0138

Alfa AF: 0.0208 Hom.: 39

Bravo AF: 0.0255

Asia WGS AF: 0.0520 AC: 181 AN: 3478

ClinVar

Significance: Benign/Likely 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

Invitae

Dec 11, 2023

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	13
Dann	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2072658; hg19: chr1-154540225;