rs3926124

Variant names:

• chr1-154569616-A-G
• rs3926124
• NM_000748.3:c.210+9A>G

Variant summary

Our verdict is Benign. The variant received -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:6
• Conservation: PhyloP100: -0.497
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• familial sleep-related hypermotor epilepsy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• autosomal dominant nocturnal frontal lobe epilepsy 3

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• autosomal dominant nocturnal frontal lobe epilepsy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 158333.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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000748.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNB2	NM_000748.3	MANE Select	c.210+9A>G		intron	N/A	NP_000739.1	P17787

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNB2	ENST00000368476.4	TSL:1 MANE Select	c.210+9A>G		intron	N/A	ENSP00000357461.3	P17787
	CHRNB2	ENST00000637900.1	TSL:5	c.210+9A>G		intron	N/A	ENSP00000490474.1	A0A1B0GVD7
	CHRNB2	ENST00000636034.1	TSL:5	n.210+9A>G		intron	N/A	ENSP00000489703.1	A0A1B0GTH5

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

GnomAD2 exomes AF: 0.0265 AC: 6650 AN: 251316 AF XY: 0.0191

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 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

African (AFR) AF: 0.366 AC: 12269 AN: 33478

American (AMR) AF: 0.0181 AC: 808 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00150 AC: 129 AN: 86256

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53358

Middle Eastern (MID) AF: 0.0203 AC: 117 AN: 5768

European-Non Finnish (NFE) AF: 0.000383 AC: 426 AN: 1111994

Other (OTH) AF: 0.0221 AC: 1333 AN: 60396

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

African (AFR) AF: 0.352 AC: 14572 AN: 41444

American (AMR) AF: 0.0288 AC: 441 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.000853 AC: 58 AN: 68008

Other (OTH) AF: 0.0621 AC: 131 AN: 2110

Alfa AF: 0.0512 Hom.: 792

Bravo AF: 0.113

Asia WGS AF: 0.0270 AC: 94 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Autosomal dominant nocturnal frontal lobe epilepsy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.5
DANN	Benign	0.62
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3926124; hg19: chr1-154542092;