chr15-32099143-G-A

Position:

• chr15-32099143-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33

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 -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	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	c.196-2160G>A		intron_variant		1	NM_000746.6	ENSP00000303727	P1

Frequencies

GnomAD3 genomes AF: 0.799 AC: 121433 AN: 151994 Hom.: 48671 Cov.: 32

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: 90 AN: 106 Hom.: 38 Cov.: 0 AF XY: 0.826 AC XY: 71 AN XY: 86

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.: 32 AF XY: 0.803 AC XY: 59691 AN XY: 74356

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

Other links and lift over

dbSNP: rs8035668; hg19: chr15-32391346;