1-154567831-A-G

Position:

• chr1-154567831-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000748.3(CHRNB2):​c.-214A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0409 in 449,844 control chromosomes in the GnomAD database, including 3,159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (2685 hom., cov: 32)
  • Exomes 𝑓: 0.011 (474 hom.)
• Consequence: CHRNB2 NM_000748.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.554

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 1-154567831-A-G is Benign according to our data. Variant chr1-154567831-A-G is described in ClinVar as [Benign]. Clinvar id is 670760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNB2	NM_000748.3	c.-214A>G		5_prime_UTR_variant	1/6	ENST00000368476.4	NP_000739.1
CHRNB2	XR_001736952.3	n.54A>G		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNB2	ENST00000368476	c.-214A>G		5_prime_UTR_variant	1/6	1	NM_000748.3	ENSP00000357461.3
CHRNB2	ENST00000636034.1	n.-214A>G		non_coding_transcript_exon_variant	1/9	5		ENSP00000489703.1
CHRNB2	ENST00000636034.1	n.-214A>G		5_prime_UTR_variant	1/9	5		ENSP00000489703.1
CHRNB2	ENST00000637900.1	c.-214A>G		upstream_gene_variant		5		ENSP00000490474.1

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15209 AN: 152064 Hom.: 2675 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0290

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.000838

Gnomad OTH AF: 0.0624

GnomAD4 exome AF: 0.0106 AC: 3163 AN: 297664 Hom.: 474 Cov.: 3 AF XY: 0.00885 AC XY: 1366 AN XY: 154414

Gnomad4 AFR exome AF: 0.349

Gnomad4 AMR exome AF: 0.0268

Gnomad4 ASJ exome AF: 0.000104

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00176

Gnomad4 FIN exome AF: 0.0000395

Gnomad4 NFE exome AF: 0.000541

Gnomad4 OTH exome AF: 0.0258

GnomAD4 genome AF: 0.100 AC: 15244 AN: 152180 Hom.: 2685 Cov.: 32 AF XY: 0.0955 AC XY: 7110 AN XY: 74420

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.0289

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000838

Gnomad4 OTH AF: 0.0622

Alfa AF: 0.0955 Hom.: 369

Bravo AF: 0.113

Asia WGS AF: 0.0270 AC: 94 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 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	-0.48
CADD	Benign	12
DANN	Benign	0.82

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: rs12062049; hg19: chr1-154540307;