15-32029282-T-C

Variant names:

• chr15-32029282-T-C
• rs3826029
• ENST00000636603.1:c.-131-1616T>C

Variant summary

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

The ENST00000636603.1(CHRNA7):​c.-131-1616T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 152,226 control chromosomes in the GnomAD database, including 41,887 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 0.73 (41887 hom., cov: 33)
• Consequence: CHRNA7 ENST00000636603.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.935
• Publications: 10 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

LOC124903441 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.822 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.-131-1616T>C		intron	N/A	ENSP00000490513.1	A0A1B0GVH2
	CHRNA7	ENST00000637183.1	TSL:5	c.-43+51088T>C		intron	N/A	ENSP00000490365.1	A0A1B0GV43
	CHRNA7	ENST00000638106.1	TSL:5	c.-378-1616T>C		intron	N/A	ENSP00000490413.1	A0A1B0GV86

Frequencies

GnomAD3 genomes AF: 0.729 AC: 110833 AN: 152108 Hom.: 41869 Cov.: 33

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.794

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.742

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

GnomAD4 genome AF: 0.728 AC: 110890 AN: 152226 Hom.: 41887 Cov.: 33 AF XY: 0.731 AC XY: 54398 AN XY: 74434

African (AFR) AF: 0.556 AC: 23084 AN: 41484

American (AMR) AF: 0.725 AC: 11093 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 2705 AN: 3472

East Asian (EAS) AF: 0.393 AC: 2034 AN: 5178

South Asian (SAS) AF: 0.793 AC: 3829 AN: 4826

European-Finnish (FIN) AF: 0.882 AC: 9372 AN: 10620

Middle Eastern (MID) AF: 0.752 AC: 218 AN: 290

European-Non Finnish (NFE) AF: 0.827 AC: 56273 AN: 68024

Other (OTH) AF: 0.738 AC: 1559 AN: 2112

Alfa AF: 0.789 Hom.: 72556

Bravo AF: 0.703

Asia WGS AF: 0.612 AC: 2132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.4
DANN	Benign	0.70
PhyloP100		-0.94

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: rs3826029;

hg19: chr15-32321485;