rs4292956

Positions:

• chr1-154576470-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 (EAS) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNB2	NM_000748.3	c.*538C>T		3_prime_UTR_variant	6/6	ENST00000368476.4
CHRNB2	XM_017000180.3	c.*538C>T		3_prime_UTR_variant	3/3
CHRNB2	XR_001736952.3	n.2314C>T		non_coding_transcript_exon_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNB2	ENST00000368476.4	c.*538C>T		3_prime_UTR_variant	6/6	1	NM_000748.3	P4
CHRNB2	ENST00000637900.1	c.*538C>T		3_prime_UTR_variant	6/6	5		A1
CHRNB2	ENST00000636034.1	c.1506-178C>T		intron_variant, NMD_transcript_variant		5

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

Gnomad4 AFR exome AF: 0.0565

Gnomad4 AMR exome AF: 0.0499

Gnomad4 ASJ exome AF: 0.0445

Gnomad4 EAS exome AF: 0.150

Gnomad4 SAS exome AF: 0.0452

Gnomad4 FIN exome AF: 0.0592

Gnomad4 NFE exome AF: 0.0632

Gnomad4 OTH exome AF: 0.0651

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

Gnomad4 AFR AF: 0.0651

Gnomad4 AMR AF: 0.0506

Gnomad4 ASJ AF: 0.0608

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.0549

Gnomad4 FIN AF: 0.0702

Gnomad4 NFE AF: 0.0719

Gnomad4 OTH AF: 0.0739

Alfa AF: 0.0708 Hom.: 64

Bravo AF: 0.0698

Asia WGS AF: 0.122 AC: 426 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	0.17
DANN	Benign	0.66

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: rs4292956; hg19: chr1-154548946;