chr15-32101457-A-AAG

Position:

• chr15-32101457-A-AAG

Variant summary

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

The NM_000746.6(CHRNA7):​c.240+111_240+112insGA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,201,912 control chromosomes in the GnomAD database, including 21,729 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (2697 hom., cov: 24)
  • Exomes 𝑓: 0.19 (19032 hom.)
• Consequence: CHRNA7 NM_000746.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.140

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 15-32101457-A-AAG is Benign according to our data. Variant chr15-32101457-A-AAG is described in ClinVar as [Benign]. Clinvar id is 1287134.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA7	NM_000746.6	c.240+111_240+112insGA		intron_variant		ENST00000306901.9	NP_000737.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA7	ENST00000306901.9	c.240+111_240+112insGA		intron_variant		1	NM_000746.6	ENSP00000303727.2

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28177 AN: 151810 Hom.: 2695 Cov.: 24

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.0662

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.196

GnomAD4 exome AF: 0.189 AC: 198729 AN: 1049984 Hom.: 19032 Cov.: 14 AF XY: 0.187 AC XY: 99395 AN XY: 531214

Gnomad4 AFR exome AF: 0.218

Gnomad4 AMR exome AF: 0.157

Gnomad4 ASJ exome AF: 0.189

Gnomad4 EAS exome AF: 0.0676

Gnomad4 SAS exome AF: 0.127

Gnomad4 FIN exome AF: 0.186

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.186

GnomAD4 genome AF: 0.186 AC: 28199 AN: 151928 Hom.: 2697 Cov.: 24 AF XY: 0.182 AC XY: 13511 AN XY: 74258

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.0663

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.194

Alfa AF: 0.0804 Hom.: 92

Asia WGS AF: 0.0850 AC: 297 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

Oct 05, 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: rs151204095; hg19: chr15-32393660;