NM_000748.3:c.1338+14G>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000748.3(CHRNB2):c.1338+14G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.086 in 1,536,424 control chromosomes in the GnomAD database, including 6,097 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.081 ( 563 hom., cov: 32)

Exomes 𝑓: 0.087 ( 5534 hom. )

Consequence

CHRNB2
NM_000748.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.531

Publications

22 publications found

Variant links:

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

CHRNB2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 1-154572175-G-T is Benign according to our data. Variant chr1-154572175-G-T is described in ClinVar as Benign. ClinVar VariationId is 158331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CHRNB2	NM_000748.3 link	c.1338+14G>T	intron_variant	Intron 5 of 5	ENST00000368476.4	NP_000739.1	P17787Q5SXY3
CHRNB2	XM_017000180.3 link	c.828+14G>T	intron_variant	Intron 2 of 2		XP_016855669.1
CHRNB2	XR_001736952.3 link	n.1605+14G>T	intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHRNB2	ENST00000368476.4 link	c.1338+14G>T	intron_variant	Intron 5 of 5	1	NM_000748.3	ENSP00000357461.3	P17787
CHRNB2	ENST00000637900.1 link	c.1344+14G>T	intron_variant	Intron 5 of 5	5		ENSP00000490474.1	A0A1B0GVD7
CHRNB2	ENST00000636034.1 link	n.1338+14G>T	intron_variant	Intron 5 of 8	5		ENSP00000489703.1	A0A1B0GTH5

Frequencies

GnomAD3 genomes

AF:

0.0808

AC:

12285

AN:

152122

Hom.:

568

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0563

Gnomad AMI

AF:

0.0747

Gnomad AMR

AF:

0.0984

Gnomad ASJ

AF:

0.136

Gnomad EAS

AF:

0.129

Gnomad SAS

AF:

0.150

Gnomad FIN

AF:

0.0555

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.0837

Gnomad OTH

AF:

0.0941

GnomAD2 exomes

AF:

0.0989

AC:

13032

AN:

131748

AF XY:

0.101

show subpopulations

Gnomad AFR exome

AF:

0.0567

Gnomad AMR exome

AF:

0.0932

Gnomad ASJ exome

AF:

0.106

Gnomad EAS exome

AF:

0.143

Gnomad FIN exome

AF:

0.0542

Gnomad NFE exome

AF:

0.0853

Gnomad OTH exome

AF:

0.104

GnomAD4 exome

AF:

0.0865

AC:

119776

AN:

1384182

Hom.:

5534

Cov.:

AF XY:

0.0881

AC XY:

60206

AN XY:

683138

show subpopulations

African (AFR)

AF:

0.0564

AC:

1779

AN:

31516

American (AMR)

AF:

0.0939

AC:

3352

AN:

35682

Ashkenazi Jewish (ASJ)

AF:

0.113

AC:

2850

AN:

25164

East Asian (EAS)

AF:

0.118

AC:

4209

AN:

35718

South Asian (SAS)

AF:

0.137

AC:

10882

AN:

79160

European-Finnish (FIN)

AF:

0.0518

AC:

1874

AN:

36152

Middle Eastern (MID)

AF:

0.145

AC:

644

AN:

4446

European-Non Finnish (NFE)

AF:

0.0824

AC:

88854

AN:

1078606

Other (OTH)

AF:

0.0923

AC:

5332

AN:

57738

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

6928

13855

20783

27710

34638

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3388

6776

10164

13552

16940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0807

AC:

12283

AN:

152242

Hom.:

563

Cov.:

AF XY:

0.0806

AC XY:

6002

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0563

AC:

2339

AN:

41556

American (AMR)

AF:

0.0984

AC:

1505

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.136

AC:

470

AN:

3468

East Asian (EAS)

AF:

0.129

AC:

668

AN:

5180

South Asian (SAS)

AF:

0.149

AC:

719

AN:

4832

European-Finnish (FIN)

AF:

0.0555

AC:

588

AN:

10602

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0837

AC:

5689

AN:

67990

Other (OTH)

AF:

0.0945

AC:

200

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

586

1172

1757

2343

2929

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

150

300

450

600

750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0835

Hom.:

103

Bravo

AF:

0.0815

Asia WGS

AF:

0.143

AC:

499

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 16, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Autosomal dominant nocturnal frontal lobe epilepsy

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.0

(source)

DANN

Benign

0.73

PhyloP100

0.53

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over