chr1-154576045-C-G

Variant names:

• chr1-154576045-C-G
• rs2072659
• NM_000748.3:c.*113C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000748.3(CHRNB2):​c.*113C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,373,202 control chromosomes in the GnomAD database, including 8,016 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.088 (731 hom., cov: 32)
  • Exomes 𝑓: 0.10 (7285 hom.)
• Consequence: CHRNB2 NM_000748.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.170
• Publications: 31 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-154576045-C-G is Benign according to our data. Variant chr1-154576045-C-G is described in ClinVar as Benign. ClinVar VariationId is 1252116.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNB2	NM_000748.3	c.*113C>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000368476.4	NP_000739.1
CHRNB2	XR_001736952.3	n.1889C>G		non_coding_transcript_exon_variant	Exon 6 of 7
CHRNB2	XM_017000180.3	c.*113C>G		3_prime_UTR_variant	Exon 3 of 3		XP_016855669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNB2	ENST00000368476.4	c.*113C>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_000748.3	ENSP00000357461.3
CHRNB2	ENST00000637900.1	c.*113C>G		3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000490474.1
CHRNB2	ENST00000636034.1	n.1505+117C>G		intron_variant	Intron 6 of 8	5		ENSP00000489703.1

Frequencies

GnomAD3 genomes AF: 0.0883 AC: 13427 AN: 152128 Hom.: 725 Cov.: 32

Gnomad AFR AF: 0.0494

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0733

Gnomad ASJ AF: 0.0634

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.0984

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0871

GnomAD4 exome AF: 0.103 AC: 125989 AN: 1220956 Hom.: 7285 Cov.: 17 AF XY: 0.105 AC XY: 64721 AN XY: 617626

African (AFR) AF: 0.0451 AC: 1301 AN: 28838

American (AMR) AF: 0.0574 AC: 2483 AN: 43246

Ashkenazi Jewish (ASJ) AF: 0.0689 AC: 1685 AN: 24466

East Asian (EAS) AF: 0.172 AC: 6589 AN: 38302

South Asian (SAS) AF: 0.134 AC: 10782 AN: 80416

European-Finnish (FIN) AF: 0.100 AC: 4201 AN: 42020

Middle Eastern (MID) AF: 0.0541 AC: 289 AN: 5342

European-Non Finnish (NFE) AF: 0.103 AC: 93212 AN: 905662

Other (OTH) AF: 0.103 AC: 5447 AN: 52664

GnomAD4 genome AF: 0.0884 AC: 13452 AN: 152246 Hom.: 731 Cov.: 32 AF XY: 0.0891 AC XY: 6632 AN XY: 74446

African (AFR) AF: 0.0497 AC: 2063 AN: 41538

American (AMR) AF: 0.0732 AC: 1120 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0634 AC: 220 AN: 3470

East Asian (EAS) AF: 0.198 AC: 1024 AN: 5164

South Asian (SAS) AF: 0.141 AC: 680 AN: 4824

European-Finnish (FIN) AF: 0.0984 AC: 1045 AN: 10620

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 7004 AN: 68004

Other (OTH) AF: 0.0923 AC: 195 AN: 2112

Alfa AF: 0.0900 Hom.: 88

Bravo AF: 0.0837

Asia WGS AF: 0.164 AC: 570 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.0
DANN	Benign	0.38
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2072659; hg19: chr1-154548521; COSMIC: COSV63807777; COSMIC: COSV63807777;