Variant rs8035668 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000746.6(CHRNA7):c.196-2160G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 152,218 control chromosomes in the GnomAD database, including 48,737 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 0.80 ( 48699 hom., cov: 32)

Exomes 𝑓: 0.85 ( 38 hom. )

Consequence

CHRNA7
NM_000746.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.33

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA7	NM_000746.6 linkuse as main transcript	c.196-2160G>A		intron_variant		ENST00000306901.9	NP_000737.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA7	ENST00000306901.9 linkuse as main transcript	c.196-2160G>A		intron_variant		1	NM_000746.6	ENSP00000303727	P1	P36544-1

Frequencies

GnomAD3 genomes

AF:

0.799

AC:

121433

AN:

151994

Hom.:

48671

Cov.:

show subpopulations

Gnomad AFR

AF:

0.741

Gnomad AMI

AF:

0.837

Gnomad AMR

AF:

0.823

Gnomad ASJ

AF:

0.820

Gnomad EAS

AF:

0.934

Gnomad SAS

AF:

0.880

Gnomad FIN

AF:

0.808

Gnomad MID

AF:

0.772

Gnomad NFE

AF:

0.810

Gnomad OTH

AF:

0.793

GnomAD4 exome

AF:

0.849

AC:

AN:

106

Hom.:

Cov.:

AF XY:

0.826

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.750

Gnomad4 AMR exome

AF:

0.500

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

0.833

Gnomad4 NFE exome

AF:

0.875

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

AF:

0.799

AC:

121512

AN:

152112

Hom.:

48699

Cov.:

AF XY:

0.803

AC XY:

59691

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.740

Gnomad4 AMR

AF:

0.823

Gnomad4 ASJ

AF:

0.820

Gnomad4 EAS

AF:

0.933

Gnomad4 SAS

AF:

0.880

Gnomad4 FIN

AF:

0.808

Gnomad4 NFE

AF:

0.810

Gnomad4 OTH

AF:

0.794

Alfa

AF:

0.806

Hom.:

67171

Bravo

AF:

0.796

Asia WGS

AF:

0.901

AC:

3131

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.090

DANN

Benign

0.48

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over