15-32101283-C-CTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000746.6(CHRNA7):c.196-6_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 0.35 (8898 hom., cov: 0)
  • Exomes 𝑓: 0.26 (1708 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHRNA7 NM_000746.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.508

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 -10 ACMG points.

• BP6: Variant 15-32101283-C-CTT is Benign according to our data. Variant chr15-32101283-C-CTT is described in ClinVar as [Benign]. Clinvar id is 1180278.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA7	NM_000746.6	c.196-6_196-5dup		intron_variant		ENST00000306901.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA7	ENST00000306901.9	c.196-6_196-5dup		intron_variant		1	NM_000746.6	P1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 49098 AN: 141220 Hom.: 8904 Cov.: 0

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.594

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.327

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.357

GnomAD3 exomes AF: 0.196 AC: 28911 AN: 147816 Hom.: 778 AF XY: 0.193 AC XY: 15743 AN XY: 81442

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.188

Gnomad ASJ exome AF: 0.185

Gnomad EAS exome AF: 0.264

Gnomad SAS exome AF: 0.167

Gnomad FIN exome AF: 0.201

Gnomad NFE exome AF: 0.200

Gnomad OTH exome AF: 0.202

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.256 AC: 326983 AN: 1277724 Hom.: 1708 Cov.: 26 AF XY: 0.254 AC XY: 161826 AN XY: 636316

Gnomad4 AFR exome AF: 0.171

Gnomad4 AMR exome AF: 0.203

Gnomad4 ASJ exome AF: 0.222

Gnomad4 EAS exome AF: 0.323

Gnomad4 SAS exome AF: 0.218

Gnomad4 FIN exome AF: 0.240

Gnomad4 NFE exome AF: 0.262

Gnomad4 OTH exome AF: 0.251

GnomAD4 genome AF: 0.348 AC: 49088 AN: 141222 Hom.: 8898 Cov.: 0 AF XY: 0.348 AC XY: 23676 AN XY: 67992

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.357

Gnomad4 EAS AF: 0.594

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.360

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

Oct 21, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs34476605; hg19: chr15-32393486;