rs8024987

Positions:

• chr15-32044027-C-G

Variant summary

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

The NM_000746.6(CHRNA7):​c.195+12990C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,168 control chromosomes in the GnomAD database, including 4,745 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 0.22 (4745 hom., cov: 33)
• Consequence: CHRNA7 NM_000746.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.815

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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA7	NM_000746.6	c.195+12990C>G		intron_variant		ENST00000306901.9
CHRNA7	NM_001190455.3	c.282+12990C>G		intron_variant
CHRNA7	XM_011521178.4	c.195+12990C>G		intron_variant
CHRNA7	NR_046324.1	n.307+12990C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA7	ENST00000306901.9	c.195+12990C>G		intron_variant		1	NM_000746.6	P1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32845 AN: 152050 Hom.: 4745 Cov.: 33

Gnomad AFR AF: 0.0492

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.203

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.216 AC: 32827 AN: 152168 Hom.: 4745 Cov.: 33 AF XY: 0.226 AC XY: 16794 AN XY: 74376

Gnomad4 AFR AF: 0.0491

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.401

Gnomad4 FIN AF: 0.427

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.200

Alfa AF: 0.260 Hom.: 748

Bravo AF: 0.185

Asia WGS AF: 0.253 AC: 878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.43
DANN	Benign	0.36

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: rs8024987; hg19: chr15-32336230;