15-32031251-A-G

Variant summary

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

The NM_000746.6(CHRNA7):c.195+214A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 151,982 control chromosomes in the GnomAD database, including 27,579 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.55 (27579 hom., cov: 31)
• Consequence: CHRNA7 NM_000746.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0140

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 15-32031251-A-G is Benign according to our data. Variant chr15-32031251-A-G is described in ClinVar as [Benign]. Clinvar id is 1246546.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA7	NM_000746.6	c.195+214A>G		intron_variant		ENST00000306901.9
CHRNA7	NM_001190455.3	c.282+214A>G		intron_variant
CHRNA7	XM_011521178.4	c.195+214A>G		intron_variant
CHRNA7	NR_046324.1	n.307+214A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA7	ENST00000306901.9	c.195+214A>G		intron_variant		1	NM_000746.6	P1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82872 AN: 151864 Hom.: 27593 Cov.: 31

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.734

Gnomad OTH AF: 0.556

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

GnomAD4 genome AF: 0.545 AC: 82842 AN: 151982 Hom.: 27579 Cov.: 31 AF XY: 0.551 AC XY: 40956 AN XY: 74292

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.665

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.692

Gnomad4 FIN AF: 0.832

Gnomad4 NFE AF: 0.734

Gnomad4 OTH AF: 0.552

Alfa AF: 0.658 Hom.: 5945

Bravo AF: 0.500

Asia WGS AF: 0.462 AC: 1610 AN: 3478

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.3
Dann	Benign	0.69

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

Other links and lift over

dbSNP: rs12908877; hg19: chr15-32323454;