ENST00000636603.1:c.-131-2134C>A

Variant names:

• chr15-32028764-C-A
• rs3087454
• ENST00000636603.1:c.-131-2134C>A

Variant summary

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

The ENST00000636603.1(CHRNA7):​c.-131-2134C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 151,996 control chromosomes in the GnomAD database, including 28,759 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 0.58 (28759 hom., cov: 31)
• Consequence: CHRNA7 ENST00000636603.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• Publications: 16 publications found

Genes affected

CHRNA7 (HGNC:1960): (cholinergic receptor nicotinic alpha 7 subunit) The nicotinic acetylcholine receptors (nAChRs) are members of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. The nAChRs are thought to be hetero-pentamers composed of homologous subunits. The proposed structure for each subunit 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. The protein encoded by this gene forms a homo-oligomeric channel, displays marked permeability to calcium ions and is a major component of brain nicotinic receptors that are blocked by, and highly sensitive to, alpha-bungarotoxin. Once this receptor binds acetylcholine, it undergoes an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. This gene is located in a region identified as a major susceptibility locus for juvenile myoclonic epilepsy and a chromosomal location involved in the genetic transmission of schizophrenia. An evolutionarily recent partial duplication event in this region results in a hybrid containing sequence from this gene and a novel FAM7A gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]

CHRNA7 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• epilepsy

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

LOC124903441 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000636603.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA7	ENST00000636603.1	TSL:5	c.-131-2134C>A		intron	N/A	ENSP00000490513.1
	CHRNA7	ENST00000637183.1	TSL:5	c.-43+50570C>A		intron	N/A	ENSP00000490365.1
	CHRNA7	ENST00000638106.1	TSL:5	c.-378-2134C>A		intron	N/A	ENSP00000490413.1

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87822 AN: 151878 Hom.: 28768 Cov.: 31

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.733

Gnomad OTH AF: 0.575

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.578 AC: 87815 AN: 151996 Hom.: 28759 Cov.: 31 AF XY: 0.582 AC XY: 43215 AN XY: 74302

African (AFR) AF: 0.300 AC: 12438 AN: 41424

American (AMR) AF: 0.534 AC: 8153 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2293 AN: 3470

East Asian (EAS) AF: 0.188 AC: 974 AN: 5180

South Asian (SAS) AF: 0.691 AC: 3326 AN: 4812

European-Finnish (FIN) AF: 0.832 AC: 8803 AN: 10582

Middle Eastern (MID) AF: 0.586 AC: 171 AN: 292

European-Non Finnish (NFE) AF: 0.733 AC: 49812 AN: 67952

Other (OTH) AF: 0.571 AC: 1206 AN: 2112

Alfa AF: 0.648 Hom.: 13128

Bravo AF: 0.537

Asia WGS AF: 0.465 AC: 1621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.35
DANN	Benign	0.37
PhyloP100		-1.7

Splicing

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

Other links and lift over

dbSNP: rs3087454; hg19: chr15-32320967;