Variant 1-154567992-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000748.3(CHRNB2):c.-53C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0866 in 1,477,526 control chromosomes in the GnomAD database, including 5,967 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.089 ( 675 hom., cov: 32)

Exomes 𝑓: 0.086 ( 5292 hom. )

Consequence

CHRNB2
NM_000748.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.486

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 1-154567992-C-T is Benign according to our data. Variant chr1-154567992-C-T is described in ClinVar as [Benign]. Clinvar id is 1291264.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-154567992-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNB2	NM_000748.3 linkuse as main transcript	c.-53C>T		5_prime_UTR_variant	1/6	ENST00000368476.4
CHRNB2	XR_001736952.3 linkuse as main transcript	n.215C>T		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
CHRNB2	ENST00000368476.4 linkuse as main transcript	c.-53C>T	5_prime_UTR_variant	1/6	1	NM_000748.3	P4
CHRNB2	ENST00000637900.1 linkuse as main transcript	c.-53C>T	5_prime_UTR_variant	1/6	5		A1
CHRNB2	ENST00000636034.1 linkuse as main transcript	c.-53C>T	5_prime_UTR_variant, NMD_transcript_variant	1/9	5

Frequencies

GnomAD3 genomes

AF:

0.0894

AC:

13595

AN:

152144

Hom.:

676

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0900

Gnomad AMI

AF:

0.0746

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.119

Gnomad SAS

AF:

0.148

Gnomad FIN

AF:

0.0551

Gnomad MID

AF:

0.150

Gnomad NFE

AF:

0.0823

Gnomad OTH

AF:

0.102

GnomAD4 exome

AF:

0.0863

AC:

114347

AN:

1325274

Hom.:

5292

Cov.:

AF XY:

0.0879

AC XY:

57434

AN XY:

653232

show subpopulations

Gnomad4 AFR exome

AF:

0.0933

Gnomad4 AMR exome

AF:

0.102

Gnomad4 ASJ exome

AF:

0.115

Gnomad4 EAS exome

AF:

0.124

Gnomad4 SAS exome

AF:

0.138

Gnomad4 FIN exome

AF:

0.0520

Gnomad4 NFE exome

AF:

0.0809

Gnomad4 OTH exome

AF:

0.0950

GnomAD4 genome

AF:

0.0893

AC:

13593

AN:

152252

Hom.:

675

Cov.:

AF XY:

0.0891

AC XY:

6630

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0899

Gnomad4 AMR

AF:

0.102

Gnomad4 ASJ

AF:

0.132

Gnomad4 EAS

AF:

0.119

Gnomad4 SAS

AF:

0.147

Gnomad4 FIN

AF:

0.0551

Gnomad4 NFE

AF:

0.0823

Gnomad4 OTH

AF:

0.103

Alfa

AF:

0.0285

Hom.:

Bravo

AF:

0.0914

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

9.5

DANN

Benign

0.76

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over