rs3087454

Variant names:

• chr15-32028764-C-A
• rs3087454
• ENST00000636603.1:c.-131-2134C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-32028764-C-A
• chr15-32028764-C-G
• chr15-32028764-C-T

Variant summary

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

The ENST00000636603.1(CHRNA7):​c.-131-2134C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 151,996 control chromosomes in the GnomAD database, including 28,759 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 0.58 (28759 hom., cov: 31)
• Consequence: CHRNA7 ENST00000636603.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• Publications: 16 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124903441	XM_047433397.1	c.573-157G>T		intron_variant	Intron 2 of 2		XP_047289353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA7	ENST00000636603.1	c.-131-2134C>A		intron_variant	Intron 1 of 9	5		ENSP00000490513.1
CHRNA7	ENST00000637183.1	c.-43+50570C>A		intron_variant	Intron 1 of 8	5		ENSP00000490365.1
CHRNA7	ENST00000638106.1	c.-378-2134C>A		intron_variant	Intron 1 of 8	5		ENSP00000490413.1
CHRNA7	ENST00000635978.1	c.-42-72539C>A		intron_variant	Intron 1 of 6	5		ENSP00000490778.1

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87822 AN: 151878 Hom.: 28768 Cov.: 31

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.733

Gnomad OTH AF: 0.575

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

GnomAD4 genome AF: 0.578 AC: 87815 AN: 151996 Hom.: 28759 Cov.: 31 AF XY: 0.582 AC XY: 43215 AN XY: 74302

African (AFR) AF: 0.300 AC: 12438 AN: 41424

American (AMR) AF: 0.534 AC: 8153 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2293 AN: 3470

East Asian (EAS) AF: 0.188 AC: 974 AN: 5180

South Asian (SAS) AF: 0.691 AC: 3326 AN: 4812

European-Finnish (FIN) AF: 0.832 AC: 8803 AN: 10582

Middle Eastern (MID) AF: 0.586 AC: 171 AN: 292

European-Non Finnish (NFE) AF: 0.733 AC: 49812 AN: 67952

Other (OTH) AF: 0.571 AC: 1206 AN: 2112

Alfa AF: 0.648 Hom.: 13128

Bravo AF: 0.537

Asia WGS AF: 0.465 AC: 1621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.35
DANN	Benign	0.37
PhyloP100		-1.7

Splicing

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

Other links and lift over

dbSNP: rs3087454; hg19: chr15-32320967;