chr15-32028764-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.65
Variant links:
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]

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ACMG classification

Classification made for transcript

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
LOC124903441XM_047433397.1 linkuse as main transcriptc.573-157G>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CHRNA7ENST00000635978.1 linkuse as main transcriptc.-42-72539C>A intron_variant 5
CHRNA7ENST00000636603.1 linkuse as main transcriptc.-131-2134C>A intron_variant 5
CHRNA7ENST00000637183.1 linkuse as main transcriptc.-43+50570C>A intron_variant 5
CHRNA7ENST00000638106.1 linkuse as main transcriptc.-378-2134C>A intron_variant 5

Frequencies

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3087454; hg19: chr15-32320967; API