Variant 15-32101283-C-CT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000746.6(CHRNA7):c.196-5dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.37 ( 9812 hom., cov: 0)

Exomes 𝑓: 0.35 ( 2312 hom. )

Failed GnomAD Quality Control

Consequence

CHRNA7
NM_000746.6 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.508

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 15-32101283-C-CT is Benign according to our data. Variant chr15-32101283-C-CT is described in ClinVar as [Benign]. Clinvar id is 1260396.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA7	NM_000746.6 linkuse as main transcript	c.196-5dup		intron_variant		ENST00000306901.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA7	ENST00000306901.9 linkuse as main transcript	c.196-5dup		intron_variant		1	NM_000746.6	P1	P36544-1

Frequencies

GnomAD3 genomes

AF:

0.367

AC:

51788

AN:

141186

Hom.:

9805

Cov.:

show subpopulations

Gnomad AFR

AF:

0.325

Gnomad AMI

AF:

0.446

Gnomad AMR

AF:

0.338

Gnomad ASJ

AF:

0.434

Gnomad EAS

AF:

0.0954

Gnomad SAS

AF:

0.250

Gnomad FIN

AF:

0.352

Gnomad MID

AF:

0.490

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.397

GnomAD3 exomes

AF:

0.347

AC:

51230

AN:

147816

Hom.:

2110

AF XY:

0.348

AC XY:

28336

AN XY:

81442

show subpopulations

Gnomad AFR exome

AF:

0.313

Gnomad AMR exome

AF:

0.295

Gnomad ASJ exome

AF:

0.354

Gnomad EAS exome

AF:

0.264

Gnomad SAS exome

AF:

0.298

Gnomad FIN exome

AF:

0.374

Gnomad NFE exome

AF:

0.378

Gnomad OTH exome

AF:

0.347

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.349

AC:

444503

AN:

1273894

Hom.:

2312

Cov.:

AF XY:

0.347

AC XY:

220125

AN XY:

634480

show subpopulations

Gnomad4 AFR exome

AF:

0.286

Gnomad4 AMR exome

AF:

0.271

Gnomad4 ASJ exome

AF:

0.348

Gnomad4 EAS exome

AF:

0.243

Gnomad4 SAS exome

AF:

0.264

Gnomad4 FIN exome

AF:

0.331

Gnomad4 NFE exome

AF:

0.364

Gnomad4 OTH exome

AF:

0.340

GnomAD4 genome

AF:

0.367

AC:

51794

AN:

141188

Hom.:

9812

Cov.:

AF XY:

0.359

AC XY:

24391

AN XY:

67986

show subpopulations

Gnomad4 AFR

AF:

0.325

Gnomad4 AMR

AF:

0.338

Gnomad4 ASJ

AF:

0.434

Gnomad4 EAS

AF:

0.0958

Gnomad4 SAS

AF:

0.250

Gnomad4 FIN

AF:

0.352

Gnomad4 NFE

AF:

0.422

Gnomad4 OTH

AF:

0.395

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 21, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over