chr15-32149331-G-T

Variant names:

• chr15-32149331-G-T
• rs2611603
• NM_000746.6:c.351-4576G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000746.6(CHRNA7):​c.351-4576G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 152,160 control chromosomes in the GnomAD database, including 41,894 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 0.73 (41894 hom., cov: 33)
• Consequence: CHRNA7 NM_000746.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• epilepsy

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000746.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA7	NM_000746.6	MANE Select	c.351-4576G>T		intron	N/A	NP_000737.1
	CHRNA7	NM_001190455.3		c.438-4576G>T		intron	N/A	NP_001177384.1
	CHRNA7	NR_046324.1		n.353-8277G>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA7	ENST00000306901.9	TSL:1 MANE Select	c.351-4576G>T		intron	N/A	ENSP00000303727.2
	CHRNA7	ENST00000454250.7	TSL:2	c.438-4576G>T		intron	N/A	ENSP00000407546.3
	CHRNA7	ENST00000675428.1		c.438-4576G>T		intron	N/A	ENSP00000502560.1

Frequencies

GnomAD3 genomes AF: 0.734 AC: 111614 AN: 152044 Hom.: 41824 Cov.: 33

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.713

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.894

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.712

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

GnomAD4 genome AF: 0.734 AC: 111740 AN: 152160 Hom.: 41894 Cov.: 33 AF XY: 0.744 AC XY: 55330 AN XY: 74390

African (AFR) AF: 0.851 AC: 35332 AN: 41540

American (AMR) AF: 0.753 AC: 11519 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2324 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5147 AN: 5156

South Asian (SAS) AF: 0.893 AC: 4315 AN: 4832

European-Finnish (FIN) AF: 0.730 AC: 7726 AN: 10578

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.633 AC: 43021 AN: 67968

Other (OTH) AF: 0.714 AC: 1509 AN: 2112

Alfa AF: 0.668 Hom.: 64014

Bravo AF: 0.746

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.061
DANN	Benign	0.48
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2611603; hg19: chr15-32441532;