1-154578556-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.*2624C>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 0.0708 in 152,378 control chromosomes in the GnomAD database, including 430 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 0.071 (430 hom., cov: 33)
  • Exomes 𝑓: 0.054 (0 hom.)
• Consequence: CHRNB2 NM_000748.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNB2	NM_000748.3	c.*2624C>T		3_prime_UTR_variant	6/6	ENST00000368476.4
CHRNB2	XM_017000180.3	c.*2624C>T		3_prime_UTR_variant	3/3
CHRNB2	XR_001736952.3	n.4029+371C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNB2	ENST00000368476.4	c.*2624C>T		3_prime_UTR_variant	6/6	1	NM_000748.3	P4
CHRNB2	ENST00000635876.1	n.537C>T		non_coding_transcript_exon_variant	2/2	5
CHRNB2	ENST00000636034.1	c.*894C>T		3_prime_UTR_variant, NMD_transcript_variant	9/9	5

Frequencies

GnomAD3 genomes AF: 0.0708 AC: 10771 AN: 152204 Hom.: 430 Cov.: 33

Gnomad AFR AF: 0.0626

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0512

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.0530

Gnomad FIN AF: 0.0716

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0737

Gnomad OTH AF: 0.0712

GnomAD4 exome AF: 0.0536 AC: 3 AN: 56 Hom.: 0 Cov.: 0 AF XY: 0.0500 AC XY: 2 AN XY: 40

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0588

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0708 AC: 10782 AN: 152322 Hom.: 430 Cov.: 33 AF XY: 0.0704 AC XY: 5247 AN XY: 74490

Gnomad4 AFR AF: 0.0626

Gnomad4 AMR AF: 0.0511

Gnomad4 ASJ AF: 0.0608

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.0530

Gnomad4 FIN AF: 0.0716

Gnomad4 NFE AF: 0.0737

Gnomad4 OTH AF: 0.0747

Alfa AF: 0.0714 Hom.: 910

Bravo AF: 0.0703

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	4.2
Dann	Benign	0.58

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: rs3811450; hg19: chr1-154551032; COSMIC: COSV105112973; COSMIC: COSV105112973;