rs3087454

Positions:

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

Variant summary

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

The XM_047433397.1(LOC124903441):​c.573-157G>T 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: LOC124903441 XM_047433397.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

Genes affected

LOC124903441 (HGNC:):

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=-0.93).
• 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/exons	MANE	UniProt
LOC124903441	XM_047433397.1	c.573-157G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA7	ENST00000635978.1	c.-42-72539C>A		intron_variant		5
CHRNA7	ENST00000636603.1	c.-131-2134C>A		intron_variant		5
CHRNA7	ENST00000637183.1	c.-43+50570C>A		intron_variant		5
CHRNA7	ENST00000638106.1	c.-378-2134C>A		intron_variant		5

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

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.691

Gnomad4 FIN AF: 0.832

Gnomad4 NFE AF: 0.733

Gnomad4 OTH AF: 0.571

Alfa AF: 0.657 Hom.: 10686

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3087454; hg19: chr15-32320967;