rs3826029

chr15-32029282-T-Cchr15-32029282-T-G

Variant summary

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

The XM_047433397.1(LOC124903441):c.572+575A>G 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: LOC124903441 XM_047433397.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.935

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124903441	XM_047433397.1	c.572+575A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA7	ENST00000635978.1	c.-42-72021T>C		intron_variant		5
CHRNA7	ENST00000636603.1	c.-131-1616T>C		intron_variant		5
CHRNA7	ENST00000637183.1	c.-43+51088T>C		intron_variant		5
CHRNA7	ENST00000638106.1	c.-378-1616T>C		intron_variant		5

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

Gnomad4 AFR AF: 0.556

Gnomad4 AMR AF: 0.725

Gnomad4 ASJ AF: 0.779

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.793

Gnomad4 FIN AF: 0.882

Gnomad4 NFE AF: 0.827

Gnomad4 OTH AF: 0.738

Alfa AF: 0.797 Hom.: 49991

Bravo AF: 0.703

Asia WGS AF: 0.612 AC: 2132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.4
Dann	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3826029; hg19: chr15-32321485;