15-32101283-CT-C

Position:

• chr15-32101283-CT-C

Variant summary

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

The NM_000746.6(CHRNA7):​c.196-5delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0322 in 1,413,606 control chromosomes in the GnomAD database, including 7 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0053 (7 hom., cov: 0)
  • Exomes 𝑓: 0.035 (0 hom.)
• Consequence: CHRNA7 NM_000746.6 splice_region, 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]

CHRNA7 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 15-32101283-CT-C is Benign according to our data. Variant chr15-32101283-CT-C is described in ClinVar as [Benign]. Clinvar id is 1243266.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA7	NM_000746.6	c.196-5delT		splice_region_variant, intron_variant		ENST00000306901.9	NP_000737.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA7	ENST00000306901.9	c.196-5delT		splice_region_variant, intron_variant		1	NM_000746.6	ENSP00000303727.2

Frequencies

GnomAD3 genomes AF: 0.00529 AC: 748 AN: 141270 Hom.: 7 Cov.: 0

Gnomad AFR AF: 0.0163

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00211

Gnomad ASJ AF: 0.000589

Gnomad EAS AF: 0.000821

Gnomad SAS AF: 0.000449

Gnomad FIN AF: 0.00395

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000686

Gnomad OTH AF: 0.00568

GnomAD3 exomes AF: 0.0653 AC: 9656 AN: 147816 Hom.: 0 AF XY: 0.0647 AC XY: 5267 AN XY: 81442

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.104

Gnomad ASJ exome AF: 0.0657

Gnomad EAS exome AF: 0.0831

Gnomad SAS exome AF: 0.103

Gnomad FIN exome AF: 0.0416

Gnomad NFE exome AF: 0.0455

Gnomad OTH exome AF: 0.0712

GnomAD4 exome AF: 0.0352 AC: 44802 AN: 1272334 Hom.: 0 Cov.: 26 AF XY: 0.0361 AC XY: 22845 AN XY: 633634

Gnomad4 AFR exome AF: 0.0830

Gnomad4 AMR exome AF: 0.0796

Gnomad4 ASJ exome AF: 0.0444

Gnomad4 EAS exome AF: 0.0499

Gnomad4 SAS exome AF: 0.0742

Gnomad4 FIN exome AF: 0.0380

Gnomad4 NFE exome AF: 0.0288

Gnomad4 OTH exome AF: 0.0394

GnomAD4 genome AF: 0.00530 AC: 749 AN: 141272 Hom.: 7 Cov.: 0 AF XY: 0.00532 AC XY: 362 AN XY: 68014

Gnomad4 AFR AF: 0.0163

Gnomad4 AMR AF: 0.00211

Gnomad4 ASJ AF: 0.000589

Gnomad4 EAS AF: 0.000824

Gnomad4 SAS AF: 0.000452

Gnomad4 FIN AF: 0.00395

Gnomad4 NFE AF: 0.000687

Gnomad4 OTH AF: 0.00565

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

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs34476605; hg19: chr15-32393486;