rs2072658

Variant names:

• chr1-154567749-G-A
• rs2072658
• ENST00000659429.2:n.7C>T

Variant summary

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

The ENST00000659429.2(ENSG00000286391):​n.7C>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: ENSG00000286391 ENST00000659429.2 non_coding_transcript_exon
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.16
• Publications: 23 publications found

Genes affected

ENSG00000286391 (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]

CHRNB2 Gene-Disease associations (from GenCC):

• familial sleep-related hypermotor epilepsy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• autosomal dominant nocturnal frontal lobe epilepsy 3

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• autosomal dominant nocturnal frontal lobe epilepsy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
CHRNB2	NM_000748.3	c.-296G>A		upstream_gene_variant		ENST00000368476.4	NP_000739.1
CHRNB2	XR_001736952.3	n.-29G>A		upstream_gene_variant
LOC107985206	XR_001738237.2	n.-32C>T		upstream_gene_variant
LOC107985206	XR_001738238.3	n.-32C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNB2	ENST00000368476.4	c.-296G>A		upstream_gene_variant		1	NM_000748.3	ENSP00000357461.3

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

African (AFR) AF: 0.00238 AC: 13 AN: 5464

American (AMR) AF: 0.0859 AC: 453 AN: 5276

Ashkenazi Jewish (ASJ) AF: 0.000921 AC: 7 AN: 7604

East Asian (EAS) AF: 0.197 AC: 3321 AN: 16832

South Asian (SAS) AF: 0.00416 AC: 40 AN: 9622

European-Finnish (FIN) AF: 0.00268 AC: 53 AN: 19784

Middle Eastern (MID) AF: 0.000867 AC: 1 AN: 1154

European-Non Finnish (NFE) AF: 0.0112 AC: 1637 AN: 146628

Other (OTH) AF: 0.0215 AC: 314 AN: 14606

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

African (AFR) AF: 0.00388 AC: 160 AN: 41220

American (AMR) AF: 0.0691 AC: 1055 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.168 AC: 866 AN: 5158

South Asian (SAS) AF: 0.00706 AC: 34 AN: 4814

European-Finnish (FIN) AF: 0.00190 AC: 20 AN: 10554

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

European-Non Finnish (NFE) AF: 0.0117 AC: 794 AN: 67946

Other (OTH) AF: 0.0138 AC: 29 AN: 2100

Alfa AF: 0.0184 Hom.: 172

Bravo AF: 0.0255

Asia WGS AF: 0.0520 AC: 181 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 14, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Autosomal dominant nocturnal frontal lobe epilepsy Benign:1

Jan 13, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: 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	-0.75
CADD	Benign	13
DANN	Benign	0.81
PhyloP100		1.2
PromoterAI		0.20	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2072658; hg19: chr1-154540225;