Genetic Variant NM_000748.3:c.*2624C>T (chr1-154578556-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.*2624C>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 0.0708 in 152,378 control chromosomes in the GnomAD database, including 430 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 0.071 ( 430 hom., cov: 33)

Exomes 𝑓: 0.054 ( 0 hom. )

Consequence

CHRNB2
NM_000748.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.178

Publications

36 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=-0.96).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.165 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.*2624C>T		3_prime_UTR	Exon 6 of 6	NP_000739.1	P17787

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHRNB2	ENST00000368476.4	TSL:1 MANE Select	c.*2624C>T	3_prime_UTR	Exon 6 of 6	ENSP00000357461.3	P17787
CHRNB2	ENST00000635876.1	TSL:5	n.537C>T	non_coding_transcript_exon	Exon 2 of 2
CHRNB2	ENST00000636034.1	TSL:5	n.*894C>T	non_coding_transcript_exon	Exon 9 of 9	ENSP00000489703.1	A0A1B0GTH5

Frequencies

GnomAD3 genomes

AF:

0.0708

AC:

10771

AN:

152204

Hom.:

430

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0626

Gnomad AMI

AF:

0.0746

Gnomad AMR

AF:

0.0512

Gnomad ASJ

AF:

0.0608

Gnomad EAS

AF:

0.175

Gnomad SAS

AF:

0.0530

Gnomad FIN

AF:

0.0716

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0737

Gnomad OTH

AF:

0.0712

GnomAD4 exome

AF:

0.0536

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0500

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0588

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0708

AC:

10782

AN:

152322

Hom.:

430

Cov.:

AF XY:

0.0704

AC XY:

5247

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.0626

AC:

2602

AN:

41568

American (AMR)

AF:

0.0511

AC:

783

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0608

AC:

211

AN:

3472

East Asian (EAS)

AF:

0.175

AC:

906

AN:

5180

South Asian (SAS)

AF:

0.0530

AC:

256

AN:

4830

European-Finnish (FIN)

AF:

0.0716

AC:

760

AN:

10616

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0737

AC:

5013

AN:

68026

Other (OTH)

AF:

0.0747

AC:

158

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

520

1041

1561

2082

2602

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

122

244

366

488

610

<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:

0.0712

Hom.:

1328

Bravo

AF:

0.0703

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

4.2

(source)

DANN

Benign

0.58

PhyloP100

-0.18

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over