dbSNP rs4292956: CHRNB2:c.*538C>T (chr1-154576470-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000748.3(CHRNB2):c.*538C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0689 in 206,726 control chromosomes in the GnomAD database, including 570 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.070 ( 427 hom., cov: 32)

Exomes 𝑓: 0.065 ( 143 hom. )

Consequence

CHRNB2
NM_000748.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.10

Publications

13 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CHRNB2	NM_000748.3 link	c.*538C>T	3_prime_UTR_variant	Exon 6 of 6	ENST00000368476.4	NP_000739.1	P17787Q5SXY3
CHRNB2	XR_001736952.3 link	n.2314C>T	non_coding_transcript_exon_variant	Exon 6 of 7
CHRNB2	XM_017000180.3 link	c.*538C>T	3_prime_UTR_variant	Exon 3 of 3		XP_016855669.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHRNB2	ENST00000368476.4 link	c.*538C>T	3_prime_UTR_variant	Exon 6 of 6	1	NM_000748.3	ENSP00000357461.3	P17787
CHRNB2	ENST00000637900.1 link	c.*538C>T	3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000490474.1	A0A1B0GVD7
CHRNB2	ENST00000636034.1 link	n.1506-178C>T	intron_variant	Intron 6 of 8	5		ENSP00000489703.1	A0A1B0GTH5

Frequencies

GnomAD3 genomes

AF:

0.0704

AC:

10713

AN:

152102

Hom.:

426

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0650

Gnomad AMI

AF:

0.0746

Gnomad AMR

AF:

0.0506

Gnomad ASJ

AF:

0.0608

Gnomad EAS

AF:

0.172

Gnomad SAS

AF:

0.0548

Gnomad FIN

AF:

0.0702

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0719

Gnomad OTH

AF:

0.0703

GnomAD4 exome

AF:

0.0646

AC:

3522

AN:

54506

Hom.:

143

Cov.:

AF XY:

0.0628

AC XY:

1770

AN XY:

28174

show subpopulations

African (AFR)

AF:

0.0565

AC:

116

AN:

2054

American (AMR)

AF:

0.0499

AC:

186

AN:

3724

Ashkenazi Jewish (ASJ)

AF:

0.0445

AC:

AN:

1190

East Asian (EAS)

AF:

0.150

AC:

501

AN:

3342

South Asian (SAS)

AF:

0.0452

AC:

311

AN:

6882

European-Finnish (FIN)

AF:

0.0592

AC:

108

AN:

1824

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

196

European-Non Finnish (NFE)

AF:

0.0632

AC:

2048

AN:

32392

Other (OTH)

AF:

0.0651

AC:

189

AN:

2902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

151

302

452

603

754

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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:

0.0705

AC:

10728

AN:

152220

Hom.:

427

Cov.:

AF XY:

0.0702

AC XY:

5222

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0651

AC:

2705

AN:

41542

American (AMR)

AF:

0.0506

AC:

774

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0608

AC:

211

AN:

3472

East Asian (EAS)

AF:

0.172

AC:

888

AN:

5156

South Asian (SAS)

AF:

0.0549

AC:

265

AN:

4830

European-Finnish (FIN)

AF:

0.0702

AC:

745

AN:

10612

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0719

AC:

4891

AN:

67988

Other (OTH)

AF:

0.0739

AC:

156

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

515

1031

1546

2062

2577

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

240

360

480

600

<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:

0.0735

Hom.:

691

Bravo

AF:

0.0698

Asia WGS

AF:

0.122

AC:

426

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.17

(source)

DANN

Benign

0.66

PhyloP100

-2.1

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

Computational scores

Splicing

Publications

Other links and lift over