rs1001555

Variant names:

• chr15-31981463-A-G
• rs1001555
• ENST00000636603.1:c.-132+14897A>G

Variant summary

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

The ENST00000636603.1(CHRNA7):​c.-132+14897A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,092 control chromosomes in the GnomAD database, including 1,031 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 0.11 (1031 hom., cov: 32)
• Consequence: CHRNA7 ENST00000636603.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.417
• Publications: 3 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA7	ENST00000636603.1	c.-132+14897A>G		intron_variant	Intron 1 of 9	5		ENSP00000490513.1
CHRNA7	ENST00000637183.1	c.-43+3269A>G		intron_variant	Intron 1 of 8	5		ENSP00000490365.1
CHRNA7	ENST00000638106.1	c.-379+14897A>G		intron_variant	Intron 1 of 8	5		ENSP00000490413.1
CHRNA7	ENST00000635978.1	c.-43+57796A>G		intron_variant	Intron 1 of 6	5		ENSP00000490778.1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 16005 AN: 151974 Hom.: 1025 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.0604

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.0922

Gnomad FIN AF: 0.0318

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.0689

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.105 AC: 16033 AN: 152092 Hom.: 1031 Cov.: 32 AF XY: 0.107 AC XY: 7955 AN XY: 74378

African (AFR) AF: 0.141 AC: 5837 AN: 41476

American (AMR) AF: 0.178 AC: 2720 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 394 AN: 3472

East Asian (EAS) AF: 0.249 AC: 1285 AN: 5152

South Asian (SAS) AF: 0.0929 AC: 447 AN: 4810

European-Finnish (FIN) AF: 0.0318 AC: 337 AN: 10604

Middle Eastern (MID) AF: 0.123 AC: 36 AN: 292

European-Non Finnish (NFE) AF: 0.0689 AC: 4686 AN: 67986

Other (OTH) AF: 0.112 AC: 236 AN: 2108

Alfa AF: 0.0808 Hom.: 785

Bravo AF: 0.117

Asia WGS AF: 0.168 AC: 585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	10
DANN	Benign	0.68
PhyloP100		0.42

Splicing

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

Other links and lift over

dbSNP: rs1001555; hg19: chr15-32273666;