NM_000748.3:c.*313T>C

Variant names:

• chr1-154576245-T-C
• rs2072660
• NM_000748.3:c.*313T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000748.3(CHRNB2):​c.*313T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 444,814 control chromosomes in the GnomAD database, including 124,117 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 0.71 (38432 hom., cov: 32)
  • Exomes 𝑓: 0.76 (85685 hom.)
• Consequence: CHRNB2 NM_000748.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54
• Publications: 43 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.782 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.*313T>C		3_prime_UTR	Exon 6 of 6	NP_000739.1	P17787

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNB2	ENST00000368476.4	TSL:1 MANE Select	c.*313T>C		3_prime_UTR	Exon 6 of 6	ENSP00000357461.3	P17787
	CHRNB2	ENST00000637900.1	TSL:5	c.*313T>C		3_prime_UTR	Exon 6 of 6	ENSP00000490474.1	A0A1B0GVD7
	CHRNB2	ENST00000636034.1	TSL:5	n.1505+317T>C		intron	N/A	ENSP00000489703.1	A0A1B0GTH5

Frequencies

GnomAD3 genomes AF: 0.706 AC: 107302 AN: 151968 Hom.: 38418 Cov.: 32

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.726

GnomAD4 exome AF: 0.764 AC: 223601 AN: 292728 Hom.: 85685 Cov.: 2 AF XY: 0.769 AC XY: 120335 AN XY: 156584

African (AFR) AF: 0.567 AC: 4822 AN: 8508

American (AMR) AF: 0.775 AC: 10506 AN: 13560

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 6769 AN: 8488

East Asian (EAS) AF: 0.749 AC: 12443 AN: 16616

South Asian (SAS) AF: 0.800 AC: 34840 AN: 43568

European-Finnish (FIN) AF: 0.716 AC: 11129 AN: 15552

Middle Eastern (MID) AF: 0.813 AC: 979 AN: 1204

European-Non Finnish (NFE) AF: 0.769 AC: 130102 AN: 169282

Other (OTH) AF: 0.753 AC: 12011 AN: 15950

GnomAD4 genome AF: 0.706 AC: 107353 AN: 152086 Hom.: 38432 Cov.: 32 AF XY: 0.707 AC XY: 52564 AN XY: 74372

African (AFR) AF: 0.562 AC: 23312 AN: 41446

American (AMR) AF: 0.759 AC: 11605 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.806 AC: 2800 AN: 3472

East Asian (EAS) AF: 0.736 AC: 3806 AN: 5174

South Asian (SAS) AF: 0.803 AC: 3871 AN: 4820

European-Finnish (FIN) AF: 0.695 AC: 7351 AN: 10580

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.768 AC: 52197 AN: 67986

Other (OTH) AF: 0.720 AC: 1521 AN: 2112

Alfa AF: 0.744 Hom.: 107984

Bravo AF: 0.703

Asia WGS AF: 0.749 AC: 2606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.39
DANN	Benign	0.79
PhyloP100		-2.5
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: rs2072660; hg19: chr1-154548721;