15-32168218-C-T

Position:

• chr15-32168218-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The ENST00000306901.9(CHRNA7):​c.1269C>T​(p.Gly423=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.38 (1257 hom., cov: 16)
  • Exomes 𝑓: 0.40 (12214 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHRNA7 ENST00000306901.9 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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]

LOC102724078 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 15-32168218-C-T is Benign according to our data. Variant chr15-32168218-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.19 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA7	NM_000746.6	c.1269C>T	p.Gly423=	synonymous_variant	10/10	ENST00000306901.9	NP_000737.1
LOC102724078	XR_007064561.1	n.963-1358G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA7	ENST00000306901.9	c.1269C>T	p.Gly423=	synonymous_variant	10/10	1	NM_000746.6	ENSP00000303727	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 43234 AN: 114438 Hom.: 1252 Cov.: 16 FAILED QC

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.377

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.398 AC: 522327 AN: 1312490 Hom.: 12214 Cov.: 40 AF XY: 0.397 AC XY: 257444 AN XY: 648578

Gnomad4 AFR exome AF: 0.356

Gnomad4 AMR exome AF: 0.379

Gnomad4 ASJ exome AF: 0.427

Gnomad4 EAS exome AF: 0.324

Gnomad4 SAS exome AF: 0.349

Gnomad4 FIN exome AF: 0.413

Gnomad4 NFE exome AF: 0.405

Gnomad4 OTH exome AF: 0.392

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.378 AC: 43274 AN: 114544 Hom.: 1257 Cov.: 16 AF XY: 0.377 AC XY: 20781 AN XY: 55128

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.375

Alfa AF: 0.303 Hom.: 253

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.94
DANN	Benign	0.59

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: rs1042724; hg19: chr15-32460419; COSMIC: COSV60967340; COSMIC: COSV60967340;