rs4292956

Variant names:

• chr1-154576470-C-T
• rs4292956
• NM_000748.3:c.*538C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000748.3(CHRNB2):​c.*538C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0689 in 206,726 control chromosomes in the GnomAD database, including 570 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.070 (427 hom., cov: 32)
  • Exomes 𝑓: 0.065 (143 hom.)
• Consequence: CHRNB2 NM_000748.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10
• Publications: 13 publications found

Genes affected

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000748.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNB2	NM_000748.3	MANE Select	c.*538C>T		3_prime_UTR	Exon 6 of 6	NP_000739.1	P17787

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNB2	ENST00000368476.4	TSL:1 MANE Select	c.*538C>T		3_prime_UTR	Exon 6 of 6	ENSP00000357461.3	P17787
	CHRNB2	ENST00000637900.1	TSL:5	c.*538C>T		3_prime_UTR	Exon 6 of 6	ENSP00000490474.1	A0A1B0GVD7
	CHRNB2	ENST00000636034.1	TSL:5	n.1506-178C>T		intron	N/A	ENSP00000489703.1	A0A1B0GTH5

Frequencies

GnomAD3 genomes AF: 0.0704 AC: 10713 AN: 152102 Hom.: 426 Cov.: 32

Gnomad AFR AF: 0.0650

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0506

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.0548

Gnomad FIN AF: 0.0702

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0719

Gnomad OTH AF: 0.0703

GnomAD4 exome AF: 0.0646 AC: 3522 AN: 54506 Hom.: 143 Cov.: 0 AF XY: 0.0628 AC XY: 1770 AN XY: 28174

African (AFR) AF: 0.0565 AC: 116 AN: 2054

American (AMR) AF: 0.0499 AC: 186 AN: 3724

Ashkenazi Jewish (ASJ) AF: 0.0445 AC: 53 AN: 1190

East Asian (EAS) AF: 0.150 AC: 501 AN: 3342

South Asian (SAS) AF: 0.0452 AC: 311 AN: 6882

European-Finnish (FIN) AF: 0.0592 AC: 108 AN: 1824

Middle Eastern (MID) AF: 0.0510 AC: 10 AN: 196

European-Non Finnish (NFE) AF: 0.0632 AC: 2048 AN: 32392

Other (OTH) AF: 0.0651 AC: 189 AN: 2902

GnomAD4 genome AF: 0.0705 AC: 10728 AN: 152220 Hom.: 427 Cov.: 32 AF XY: 0.0702 AC XY: 5222 AN XY: 74422

African (AFR) AF: 0.0651 AC: 2705 AN: 41542

American (AMR) AF: 0.0506 AC: 774 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 211 AN: 3472

East Asian (EAS) AF: 0.172 AC: 888 AN: 5156

South Asian (SAS) AF: 0.0549 AC: 265 AN: 4830

European-Finnish (FIN) AF: 0.0702 AC: 745 AN: 10612

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0719 AC: 4891 AN: 67988

Other (OTH) AF: 0.0739 AC: 156 AN: 2112

Alfa AF: 0.0735 Hom.: 691

Bravo AF: 0.0698

Asia WGS AF: 0.122 AC: 426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.17
DANN	Benign	0.66
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs4292956; hg19: chr1-154548946;