NM_000748.3:c.-51C>T

Variant names:

• chr1-154567994-C-T
• rs111862660
• NM_000748.3:c.-51C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000748.3(CHRNB2):​c.-51C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000226 in 1,328,380 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: CHRNB2 NM_000748.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454
• Publications: 1 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

ENSG00000286391 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNB2	NM_000748.3	c.-51C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6	ENST00000368476.4	NP_000739.1
CHRNB2	NM_000748.3	c.-51C>T		5_prime_UTR_variant	Exon 1 of 6	ENST00000368476.4	NP_000739.1
CHRNB2	XR_001736952.3	n.217C>T		non_coding_transcript_exon_variant	Exon 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNB2	ENST00000368476.4	c.-51C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6	1	NM_000748.3	ENSP00000357461.3
CHRNB2	ENST00000368476.4	c.-51C>T		5_prime_UTR_variant	Exon 1 of 6	1	NM_000748.3	ENSP00000357461.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000226 AC: 3 AN: 1328380 Hom.: 0 Cov.: 29 AF XY: 0.00000305 AC XY: 2 AN XY: 654912

African (AFR) AF: 0.00 AC: 0 AN: 27218

American (AMR) AF: 0.00 AC: 0 AN: 27362

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22730

East Asian (EAS) AF: 0.00 AC: 0 AN: 30870

South Asian (SAS) AF: 0.00 AC: 0 AN: 72474

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4424

European-Non Finnish (NFE) AF: 0.00000285 AC: 3 AN: 1051832

Other (OTH) AF: 0.00 AC: 0 AN: 55154

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.2
DANN	Benign	0.84
PhyloP100		-0.45
PromoterAI		-0.018	Neutral

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: rs111862660; hg19: chr1-154540470;