rs2072661

Variant names:

• chr1-154576404-G-A
• rs2072661
• NM_000748.3:c.*472G>A

Variant summary

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

The NM_000748.3(CHRNB2):​c.*472G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 269,082 control chromosomes in the GnomAD database, including 8,021 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 0.25 (4812 hom., cov: 32)
  • Exomes 𝑓: 0.23 (3209 hom.)
• Consequence: CHRNB2 NM_000748.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.562
• Publications: 43 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.276 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.*472G>A		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.*472G>A		3_prime_UTR	Exon 6 of 6	ENSP00000357461.3	P17787
	CHRNB2	ENST00000637900.1	TSL:5	c.*472G>A		3_prime_UTR	Exon 6 of 6	ENSP00000490474.1	A0A1B0GVD7
	CHRNB2	ENST00000636034.1	TSL:5	n.1506-244G>A		intron	N/A	ENSP00000489703.1	A0A1B0GTH5

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38504 AN: 151980 Hom.: 4804 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.247

GnomAD4 exome AF: 0.231 AC: 27078 AN: 116984 Hom.: 3209 Cov.: 0 AF XY: 0.227 AC XY: 14090 AN XY: 61990

African (AFR) AF: 0.277 AC: 1141 AN: 4120

American (AMR) AF: 0.219 AC: 1160 AN: 5288

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 601 AN: 2876

East Asian (EAS) AF: 0.278 AC: 1553 AN: 5594

South Asian (SAS) AF: 0.195 AC: 3784 AN: 19448

European-Finnish (FIN) AF: 0.279 AC: 1441 AN: 5160

Middle Eastern (MID) AF: 0.206 AC: 93 AN: 452

European-Non Finnish (NFE) AF: 0.234 AC: 15871 AN: 67968

Other (OTH) AF: 0.236 AC: 1434 AN: 6078

GnomAD4 genome AF: 0.253 AC: 38540 AN: 152098 Hom.: 4812 Cov.: 32 AF XY: 0.254 AC XY: 18860 AN XY: 74360

African (AFR) AF: 0.281 AC: 11641 AN: 41484

American (AMR) AF: 0.233 AC: 3568 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 671 AN: 3472

East Asian (EAS) AF: 0.281 AC: 1450 AN: 5162

South Asian (SAS) AF: 0.198 AC: 957 AN: 4828

European-Finnish (FIN) AF: 0.304 AC: 3221 AN: 10586

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16162 AN: 67970

Other (OTH) AF: 0.252 AC: 532 AN: 2108

Alfa AF: 0.245 Hom.: 2374

Bravo AF: 0.251

Asia WGS AF: 0.259 AC: 898 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.2
DANN	Benign	0.71
PhyloP100		0.56
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: rs2072661; hg19: chr1-154548880;