rs1514246

Variant names:

• chr15-32027287-A-C
• rs1514246
• ENST00000636603.1:c.-131-3611A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000636603.1(CHRNA7):​c.-131-3611A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 152,080 control chromosomes in the GnomAD database, including 29,576 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 0.59 (29576 hom., cov: 32)
• Consequence: CHRNA7 ENST00000636603.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• epilepsy

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000636603.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA7	ENST00000636603.1	TSL:5	c.-131-3611A>C		intron	N/A	ENSP00000490513.1	A0A1B0GVH2
	CHRNA7	ENST00000637183.1	TSL:5	c.-43+49093A>C		intron	N/A	ENSP00000490365.1	A0A1B0GV43
	CHRNA7	ENST00000638106.1	TSL:5	c.-378-3611A>C		intron	N/A	ENSP00000490413.1	A0A1B0GV86

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89985 AN: 151962 Hom.: 29580 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.592 AC: 89992 AN: 152080 Hom.: 29576 Cov.: 32 AF XY: 0.596 AC XY: 44293 AN XY: 74330

African (AFR) AF: 0.342 AC: 14182 AN: 41466

American (AMR) AF: 0.542 AC: 8278 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2292 AN: 3470

East Asian (EAS) AF: 0.193 AC: 1001 AN: 5176

South Asian (SAS) AF: 0.696 AC: 3349 AN: 4814

European-Finnish (FIN) AF: 0.838 AC: 8865 AN: 10576

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.735 AC: 49974 AN: 67976

Other (OTH) AF: 0.585 AC: 1236 AN: 2112

Alfa AF: 0.668 Hom.: 4458

Bravo AF: 0.553

Asia WGS AF: 0.473 AC: 1648 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.3
DANN	Benign	0.59
PhyloP100		0.23

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1514246;

hg19: chr15-32319490;