15-32125837-A-G

Position:

• chr15-32125837-A-G

Variant summary

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

The NM_000746.6(CHRNA7):​c.350+13938A>G 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 151,972 control chromosomes in the GnomAD database, including 25,534 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 (25534 hom., cov: 31)
• Consequence: CHRNA7 NM_000746.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.743

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• 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	Protein	UniProt
CHRNA7	NM_000746.6	c.350+13938A>G		intron_variant		ENST00000306901.9	NP_000737.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA7	ENST00000306901.9	c.350+13938A>G		intron_variant		1	NM_000746.6	ENSP00000303727.2

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86834 AN: 151852 Hom.: 25486 Cov.: 31

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.572 AC: 86933 AN: 151972 Hom.: 25534 Cov.: 31 AF XY: 0.574 AC XY: 42651 AN XY: 74288

Gnomad4 AFR AF: 0.704

Gnomad4 AMR AF: 0.581

Gnomad4 ASJ AF: 0.552

Gnomad4 EAS AF: 0.701

Gnomad4 SAS AF: 0.691

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.569

Alfa AF: 0.510 Hom.: 30938

Bravo AF: 0.585

Asia WGS AF: 0.728 AC: 2530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.67

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: rs904951; hg19: chr15-32418038;