1-154567992-C-T

Position:

• chr1-154567992-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.486

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
CHRNB2	NM_000748.3	c.-53C>T		5_prime_UTR_variant	1/6	ENST00000368476.4	NP_000739.1
CHRNB2	XR_001736952.3	n.215C>T		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNB2	ENST00000368476	c.-53C>T		5_prime_UTR_variant	1/6	1	NM_000748.3	ENSP00000357461.3
CHRNB2	ENST00000637900	c.-53C>T		5_prime_UTR_variant	1/6	5		ENSP00000490474.1
CHRNB2	ENST00000636034.1	n.-53C>T		non_coding_transcript_exon_variant	1/9	5		ENSP00000489703.1
CHRNB2	ENST00000636034.1	n.-53C>T		5_prime_UTR_variant	1/9	5		ENSP00000489703.1

Frequencies

GnomAD3 genomes AF: 0.0894 AC: 13595 AN: 152144 Hom.: 676 Cov.: 32

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.: 28 AF XY: 0.0879 AC XY: 57434 AN XY: 653232

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.: 32 AF XY: 0.0891 AC XY: 6630 AN XY: 74426

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.: 21

Bravo AF: 0.0914

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

Other links and lift over

dbSNP: rs2280781; hg19: chr1-154540468; COSMIC: COSV63809242; COSMIC: COSV63809242;