rs3926124

Positions:

• chr1-154569616-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.210+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0188 in 1,613,970 control chromosomes in the GnomAD database, including 5,064 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (2683 hom., cov: 31)
  • Exomes 𝑓: 0.010 (2381 hom.)
• Consequence: CHRNB2 NM_000748.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.497

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=-0.9).
• BP6: Variant 1-154569616-A-G is Benign according to our data. Variant chr1-154569616-A-G is described in ClinVar as [Benign]. Clinvar id is 158333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-154569616-A-G is described in Lovd as [Likely_benign].
• 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.210+9A>G		intron_variant		ENST00000368476.4	NP_000739.1
CHRNB2	XR_001736952.3	n.477+9A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNB2	ENST00000368476.4	c.210+9A>G		intron_variant		1	NM_000748.3	ENSP00000357461.3
CHRNB2	ENST00000637900.1	c.210+9A>G		intron_variant		5		ENSP00000490474.1
CHRNB2	ENST00000636034.1	n.210+9A>G		intron_variant		5		ENSP00000489703.1
CHRNB2	ENST00000636695.1	n.80+9A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0999 AC: 15189 AN: 152044 Hom.: 2673 Cov.: 31

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0289

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: 0.000853

Gnomad OTH AF: 0.0623

GnomAD3 exomes AF: 0.0265 AC: 6650 AN: 251316 Hom.: 1113 AF XY: 0.0191 AC XY: 2600 AN XY: 135854

Gnomad AFR exome AF: 0.364

Gnomad AMR exome AF: 0.0161

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00114

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.000712

Gnomad OTH exome AF: 0.0114

GnomAD4 exome AF: 0.0103 AC: 15087 AN: 1461808 Hom.: 2381 Cov.: 34 AF XY: 0.00887 AC XY: 6450 AN XY: 727212

Gnomad4 AFR exome AF: 0.366

Gnomad4 AMR exome AF: 0.0181

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00150

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000383

Gnomad4 OTH exome AF: 0.0221

GnomAD4 genome AF: 0.100 AC: 15224 AN: 152162 Hom.: 2683 Cov.: 31 AF XY: 0.0954 AC XY: 7098 AN XY: 74416

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.0288

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000853

Gnomad4 OTH AF: 0.0621

Alfa AF: 0.0527 Hom.: 608

Bravo AF: 0.113

Asia WGS AF: 0.0270 AC: 94 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autosomal dominant nocturnal frontal lobe epilepsy Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.5
DANN	Benign	0.62

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: rs3926124; hg19: chr1-154542092;