15-32030509-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The XM_047433397.1(LOC124903441):c.40+48G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0481 in 1,286,654 control chromosomes in the GnomAD database, including 1,607 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (134 hom., cov: 31)
  • Exomes 𝑓: 0.050 (1473 hom.)
• Consequence: LOC124903441 XM_047433397.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.447

Genes affected

LOC124903441 (HGNC:):

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 15-32030509-C-T is Benign according to our data. Variant chr15-32030509-C-T is described in ClinVar as [Benign]. Clinvar id is 1235884.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124903441	XM_047433397.1	c.40+48G>A		intron_variant
CHRNA7	NM_000746.6			upstream_gene_variant		ENST00000306901.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA7	ENST00000306901.9			upstream_gene_variant		1	NM_000746.6	P1

Frequencies

GnomAD3 genomes AF: 0.0347 AC: 5233 AN: 150706 Hom.: 134 Cov.: 31

Gnomad AFR AF: 0.00955

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.0334

Gnomad ASJ AF: 0.0517

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0278

Gnomad FIN AF: 0.0273

Gnomad MID AF: 0.0641

Gnomad NFE AF: 0.0529

Gnomad OTH AF: 0.0386

GnomAD4 exome AF: 0.0498 AC: 56610 AN: 1135846 Hom.: 1473 Cov.: 19 AF XY: 0.0494 AC XY: 27168 AN XY: 549670

Gnomad4 AFR exome AF: 0.00778

Gnomad4 AMR exome AF: 0.0319

Gnomad4 ASJ exome AF: 0.0455

Gnomad4 EAS exome AF: 0.000153

Gnomad4 SAS exome AF: 0.0335

Gnomad4 FIN exome AF: 0.0307

Gnomad4 NFE exome AF: 0.0539

Gnomad4 OTH exome AF: 0.0473

GnomAD4 genome AF: 0.0347 AC: 5231 AN: 150808 Hom.: 134 Cov.: 31 AF XY: 0.0337 AC XY: 2485 AN XY: 73668

Gnomad4 AFR AF: 0.00952

Gnomad4 AMR AF: 0.0334

Gnomad4 ASJ AF: 0.0517

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0285

Gnomad4 FIN AF: 0.0273

Gnomad4 NFE AF: 0.0529

Gnomad4 OTH AF: 0.0378

Alfa AF: 0.0459 Hom.: 28

Bravo AF: 0.0347

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

This variant is associated with the following publications: (PMID: 12470124) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.4
Dann	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs149637464; hg19: chr15-32322712;