1-154567990-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000748.3(CHRNB2):c.-55C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0041 in 1,470,084 control chromosomes in the GnomAD database, including 232 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (143 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (89 hom.)
• Consequence: CHRNB2 NM_000748.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.202

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 1-154567990-C-T is Benign according to our data. Variant chr1-154567990-C-T is described in ClinVar as [Benign]. Clinvar id is 670849.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNB2	NM_000748.3	c.-55C>T		5_prime_UTR_variant	1/6	ENST00000368476.4
CHRNB2	XR_001736952.3	n.213C>T		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNB2	ENST00000368476.4	c.-55C>T		5_prime_UTR_variant	1/6	1	NM_000748.3	P4
CHRNB2	ENST00000637900.1	c.-55C>T		5_prime_UTR_variant	1/6	5		A1
CHRNB2	ENST00000636034.1	c.-55C>T		5_prime_UTR_variant, NMD_transcript_variant	1/9	5

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 3401 AN: 152174 Hom.: 142 Cov.: 32

Gnomad AFR AF: 0.0793

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00860

GnomAD4 exome AF: 0.00199 AC: 2617 AN: 1317802 Hom.: 89 Cov.: 27 AF XY: 0.00166 AC XY: 1077 AN XY: 649358

Gnomad4 AFR exome AF: 0.0828

Gnomad4 AMR exome AF: 0.00354

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000326

Gnomad4 SAS exome AF: 0.000282

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000287

Gnomad4 OTH exome AF: 0.00435

GnomAD4 genome AF: 0.0224 AC: 3410 AN: 152282 Hom.: 143 Cov.: 32 AF XY: 0.0207 AC XY: 1538 AN XY: 74456

Gnomad4 AFR AF: 0.0793

Gnomad4 AMR AF: 0.00529

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.0173 Hom.: 18

Bravo AF: 0.0242

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	12
Dann	Benign	0.76

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: rs55799808; hg19: chr1-154540466;