rs2072661

Positions:

• chr1-154576404-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNB2	NM_000748.3	c.*472G>A		3_prime_UTR_variant	6/6	ENST00000368476.4	NP_000739.1
CHRNB2	XM_017000180.3	c.*472G>A		3_prime_UTR_variant	3/3		XP_016855669.1
CHRNB2	XR_001736952.3	n.2248G>A		non_coding_transcript_exon_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNB2	ENST00000368476.4	c.*472G>A		3_prime_UTR_variant	6/6	1	NM_000748.3	ENSP00000357461.3
CHRNB2	ENST00000637900.1	c.*472G>A		3_prime_UTR_variant	6/6	5		ENSP00000490474.1
CHRNB2	ENST00000636034.1	n.1506-244G>A		intron_variant		5		ENSP00000489703.1

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

Gnomad4 AFR exome AF: 0.277

Gnomad4 AMR exome AF: 0.219

Gnomad4 ASJ exome AF: 0.209

Gnomad4 EAS exome AF: 0.278

Gnomad4 SAS exome AF: 0.195

Gnomad4 FIN exome AF: 0.279

Gnomad4 NFE exome AF: 0.234

Gnomad4 OTH exome AF: 0.236

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

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.252

Alfa AF: 0.247 Hom.: 914

Bravo AF: 0.251

Asia WGS AF: 0.259 AC: 898 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.2
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs2072661; hg19: chr1-154548880;