chr15-32126544-C-T

Position:

• chr15-32126544-C-T

Variant summary

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

The NM_000746.6(CHRNA7):​c.350+14645C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 152,026 control chromosomes in the GnomAD database, including 25,550 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 0.57 (25550 hom., cov: 32)
• Consequence: CHRNA7 NM_000746.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA7	NM_000746.6	c.350+14645C>T		intron_variant		ENST00000306901.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA7	ENST00000306901.9	c.350+14645C>T		intron_variant		1	NM_000746.6	P1

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86871 AN: 151908 Hom.: 25505 Cov.: 32

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.569

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

GnomAD4 genome AF: 0.572 AC: 86964 AN: 152026 Hom.: 25550 Cov.: 32 AF XY: 0.574 AC XY: 42651 AN XY: 74280

Gnomad4 AFR AF: 0.704

Gnomad4 AMR AF: 0.581

Gnomad4 ASJ AF: 0.547

Gnomad4 EAS AF: 0.701

Gnomad4 SAS AF: 0.691

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.565

Alfa AF: 0.550 Hom.: 3926

Bravo AF: 0.585

Asia WGS AF: 0.726 AC: 2524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.3
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs904952; hg19: chr15-32418745;