rs1514246

chr15-32027287-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000636603.1(CHRNA7):c.-131-3611A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 152,080 control chromosomes in the GnomAD database, including 29,576 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 0.59 (29576 hom., cov: 32)
• Consequence: CHRNA7 ENST00000636603.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA7	ENST00000635978.1	c.-42-74016A>C		intron_variant		5
CHRNA7	ENST00000636603.1	c.-131-3611A>C		intron_variant		5
CHRNA7	ENST00000637183.1	c.-43+49093A>C		intron_variant		5
CHRNA7	ENST00000638106.1	c.-378-3611A>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89985 AN: 151962 Hom.: 29580 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.592 AC: 89992 AN: 152080 Hom.: 29576 Cov.: 32 AF XY: 0.596 AC XY: 44293 AN XY: 74330

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.542

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.696

Gnomad4 FIN AF: 0.838

Gnomad4 NFE AF: 0.735

Gnomad4 OTH AF: 0.585

Alfa AF: 0.632 Hom.: 2997

Bravo AF: 0.553

Asia WGS AF: 0.473 AC: 1648 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	2.3
Dann	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1514246; hg19: chr15-32319490;