ENST00000524096.5:c.-231C>A

Variant names:

• chr8-27479863-G-T
• rs2565055
• ENST00000524096.5:c.-231C>A

Variant summary

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

The ENST00000524096.5(CHRNA2):​c.-231C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 151,940 control chromosomes in the GnomAD database, including 5,660 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 0.27 (5654 hom., cov: 31)
  • Exomes 𝑓: 0.27 (6 hom.)
• Consequence: CHRNA2 ENST00000524096.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660
• Publications: 10 publications found

Genes affected

CHRNA2 (HGNC:1956): (cholinergic receptor nicotinic alpha 2 subunit) Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels formed by a pentameric arrangement of alpha and beta subunits to create distinct muscle and neuronal receptors. Neuronal receptors are found throughout the peripheral and central nervous system where they are involved in fast synaptic transmission. This gene encodes an alpha subunit that is widely expressed in the brain. The proposed structure for nAChR subunits is a conserved N-terminal extracellular domain followed by three conserved transmembrane domains, a variable cytoplasmic loop, a fourth conserved transmembrane domain, and a short C-terminal extracellular region. Mutations in this gene cause autosomal dominant nocturnal frontal lobe epilepsy type 4. Single nucleotide polymorphisms (SNPs) in this gene have been associated with nicotine dependence. [provided by RefSeq, Nov 2009]

CHRNA2 Gene-Disease associations (from GenCC):

• autosomal dominant nocturnal frontal lobe epilepsy 4

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Illumina, Labcorp Genetics (formerly Invitae)
• autosomal dominant nocturnal frontal lobe epilepsy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial sleep-related hypermotor epilepsy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• benign familial infantile epilepsy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000524096.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA2	ENST00000524096.5	TSL:4	c.-231C>A		5_prime_UTR	Exon 1 of 4	ENSP00000430422.1
	CHRNA2	ENST00000520208.1	TSL:4	c.-527C>A		upstream_gene	N/A	ENSP00000430994.1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40792 AN: 151736 Hom.: 5645 Cov.: 31

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.261

GnomAD4 exome AF: 0.267 AC: 23 AN: 86 Hom.: 6 Cov.: 0 AF XY: 0.271 AC XY: 13 AN XY: 48

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 3 AN: 4

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.429 AC: 6 AN: 14

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.232 AC: 13 AN: 56

Other (OTH) AF: 0.100 AC: 1 AN: 10

GnomAD4 genome AF: 0.269 AC: 40840 AN: 151854 Hom.: 5654 Cov.: 31 AF XY: 0.271 AC XY: 20116 AN XY: 74194

African (AFR) AF: 0.310 AC: 12830 AN: 41392

American (AMR) AF: 0.253 AC: 3856 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1030 AN: 3470

East Asian (EAS) AF: 0.228 AC: 1180 AN: 5170

South Asian (SAS) AF: 0.211 AC: 1011 AN: 4800

European-Finnish (FIN) AF: 0.356 AC: 3745 AN: 10530

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16391 AN: 67938

Other (OTH) AF: 0.258 AC: 542 AN: 2102

Alfa AF: 0.251 Hom.: 6451

Bravo AF: 0.264

Asia WGS AF: 0.228 AC: 795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.79
PhyloP100		-0.066
PromoterAI		-0.0028	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2565055; hg19: chr8-27337380;