rs12062049

Variant names:

• chr1-154567831-A-G
• rs12062049
• NM_000748.3:c.-214A>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.-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
• Publications: 3 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: Labcorp Genetics (formerly Invitae), G2P
• autosomal dominant nocturnal frontal lobe epilepsy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000286391 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.-214A>G		5_prime_UTR	Exon 1 of 6	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.-214A>G		5_prime_UTR	Exon 1 of 6	ENSP00000357461.3	P17787
	CHRNB2	ENST00000636034.1	TSL:5	n.-214A>G		non_coding_transcript_exon	Exon 1 of 9	ENSP00000489703.1	A0A1B0GTH5
	ENSG00000286391	ENST00000820231.1		n.98T>C		non_coding_transcript_exon	Exon 1 of 2

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

African (AFR) AF: 0.349 AC: 2342 AN: 6714

American (AMR) AF: 0.0268 AC: 186 AN: 6934

Ashkenazi Jewish (ASJ) AF: 0.000104 AC: 1 AN: 9576

East Asian (EAS) AF: 0.00 AC: 0 AN: 21354

South Asian (SAS) AF: 0.00176 AC: 30 AN: 17052

European-Finnish (FIN) AF: 0.0000395 AC: 1 AN: 25336

Middle Eastern (MID) AF: 0.0117 AC: 17 AN: 1454

European-Non Finnish (NFE) AF: 0.000541 AC: 103 AN: 190542

Other (OTH) AF: 0.0258 AC: 483 AN: 18702

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

African (AFR) AF: 0.352 AC: 14592 AN: 41476

American (AMR) AF: 0.0289 AC: 442 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.000838 AC: 57 AN: 68010

Other (OTH) AF: 0.0622 AC: 131 AN: 2106

Alfa AF: 0.0727 Hom.: 558

Bravo AF: 0.113

Asia WGS AF: 0.0270 AC: 94 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	12
DANN	Benign	0.82
PhyloP100		-0.55
PromoterAI		0.071	Neutral
Mutation Taster		=298/2	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: rs12062049; hg19: chr1-154540307;