chr1-154572175-G-T

Position:

• chr1-154572175-G-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.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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.531

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=-0.85).
• BP6: Variant 1-154572175-G-T is Benign according to our data. Variant chr1-154572175-G-T is described in ClinVar as [Benign]. Clinvar id is 158331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-154572175-G-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNB2	NM_000748.3	c.1338+14G>T		intron_variant		ENST00000368476.4	NP_000739.1
CHRNB2	XM_017000180.3	c.828+14G>T		intron_variant			XP_016855669.1
CHRNB2	XR_001736952.3	n.1605+14G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNB2	ENST00000368476.4	c.1338+14G>T		intron_variant		1	NM_000748.3	ENSP00000357461.3
CHRNB2	ENST00000637900.1	c.1344+14G>T		intron_variant		5		ENSP00000490474.1
CHRNB2	ENST00000636034.1	n.1338+14G>T		intron_variant		5		ENSP00000489703.1

Frequencies

GnomAD3 genomes AF: 0.0808 AC: 12285 AN: 152122 Hom.: 568 Cov.: 32

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

GnomAD3 exomes AF: 0.0989 AC: 13032 AN: 131748 Hom.: 734 AF XY: 0.101 AC XY: 7300 AN XY: 71934

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 SAS exome AF: 0.136

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.: 34 AF XY: 0.0881 AC XY: 60206 AN XY: 683138

Gnomad4 AFR exome AF: 0.0564

Gnomad4 AMR exome AF: 0.0939

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.118

Gnomad4 SAS exome AF: 0.137

Gnomad4 FIN exome AF: 0.0518

Gnomad4 NFE exome AF: 0.0824

Gnomad4 OTH exome AF: 0.0923

GnomAD4 genome AF: 0.0807 AC: 12283 AN: 152242 Hom.: 563 Cov.: 32 AF XY: 0.0806 AC XY: 6002 AN XY: 74444

Gnomad4 AFR AF: 0.0563

Gnomad4 AMR AF: 0.0984

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.0555

Gnomad4 NFE AF: 0.0837

Gnomad4 OTH AF: 0.0945

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

Submissions by phenotype

not specified Benign:3

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 16, 2016	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autosomal dominant nocturnal frontal lobe epilepsy Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.73

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: rs4845378; hg19: chr1-154544651; COSMIC: COSV63809549; COSMIC: COSV63809549;