rs2072660

Positions:

• chr1-154576245-T-C
• chr1-154576245-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000748.3(CHRNB2):​c.*313T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 444,814 control chromosomes in the GnomAD database, including 124,117 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 0.71 (38432 hom., cov: 32)
  • Exomes 𝑓: 0.76 (85685 hom.)
• Consequence: CHRNB2 NM_000748.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNB2	NM_000748.3	c.*313T>C		3_prime_UTR_variant	6/6	ENST00000368476.4
CHRNB2	XM_017000180.3	c.*313T>C		3_prime_UTR_variant	3/3
CHRNB2	XR_001736952.3	n.2089T>C		non_coding_transcript_exon_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNB2	ENST00000368476.4	c.*313T>C		3_prime_UTR_variant	6/6	1	NM_000748.3	P4
CHRNB2	ENST00000637900.1	c.*313T>C		3_prime_UTR_variant	6/6	5		A1
CHRNB2	ENST00000636034.1	c.1505+317T>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.706 AC: 107302 AN: 151968 Hom.: 38418 Cov.: 32

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.726

GnomAD4 exome AF: 0.764 AC: 223601 AN: 292728 Hom.: 85685 Cov.: 2 AF XY: 0.769 AC XY: 120335 AN XY: 156584

Gnomad4 AFR exome AF: 0.567

Gnomad4 AMR exome AF: 0.775

Gnomad4 ASJ exome AF: 0.797

Gnomad4 EAS exome AF: 0.749

Gnomad4 SAS exome AF: 0.800

Gnomad4 FIN exome AF: 0.716

Gnomad4 NFE exome AF: 0.769

Gnomad4 OTH exome AF: 0.753

GnomAD4 genome AF: 0.706 AC: 107353 AN: 152086 Hom.: 38432 Cov.: 32 AF XY: 0.707 AC XY: 52564 AN XY: 74372

Gnomad4 AFR AF: 0.562

Gnomad4 AMR AF: 0.759

Gnomad4 ASJ AF: 0.806

Gnomad4 EAS AF: 0.736

Gnomad4 SAS AF: 0.803

Gnomad4 FIN AF: 0.695

Gnomad4 NFE AF: 0.768

Gnomad4 OTH AF: 0.720

Alfa AF: 0.753 Hom.: 39244

Bravo AF: 0.703

Asia WGS AF: 0.749 AC: 2606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.39
DANN	Benign	0.79

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: rs2072660; hg19: chr1-154548721;