15-31925237-A-T

Variant names:

• chr15-31925237-A-T
• rs953325
• ENST00000635978.1:c.-43+1570A>T

Variant summary

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

The ENST00000635978.1(CHRNA7):​c.-43+1570A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 152,050 control chromosomes in the GnomAD database, including 38,409 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 (38409 hom., cov: 32)
• Consequence: CHRNA7 ENST00000635978.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.446
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.824 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	ENST00000635978.1	c.-43+1570A>T		intron_variant	Intron 1 of 6	5		ENSP00000490778.1

Frequencies

GnomAD3 genomes AF: 0.711 AC: 108023 AN: 151932 Hom.: 38369 Cov.: 32

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.745

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.695

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

GnomAD4 genome AF: 0.711 AC: 108112 AN: 152050 Hom.: 38409 Cov.: 32 AF XY: 0.716 AC XY: 53179 AN XY: 74320

African (AFR) AF: 0.726 AC: 30092 AN: 41476

American (AMR) AF: 0.714 AC: 10905 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2187 AN: 3466

East Asian (EAS) AF: 0.845 AC: 4365 AN: 5164

South Asian (SAS) AF: 0.745 AC: 3592 AN: 4820

European-Finnish (FIN) AF: 0.762 AC: 8052 AN: 10566

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.686 AC: 46629 AN: 67964

Other (OTH) AF: 0.697 AC: 1470 AN: 2110

Alfa AF: 0.692 Hom.: 4503

Bravo AF: 0.709

Asia WGS AF: 0.790 AC: 2750 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.23
DANN	Benign	0.55
PhyloP100		-0.45

Splicing

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

Other links and lift over

dbSNP: rs953325; hg19: chr15-32217440;