rs6494165

Variant names:

• chr15-32029083-T-G
• rs6494165
• ENST00000636603.1:c.-131-1815T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000636603.1(CHRNA7):​c.-131-1815T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0589 in 152,248 control chromosomes in the GnomAD database, including 333 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 0.059 (333 hom., cov: 32)
• Consequence: CHRNA7 ENST00000636603.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• epilepsy

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

LOC124903441 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124903441	XM_047433397.1	c.573-476A>C		intron_variant	Intron 2 of 2		XP_047289353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA7	ENST00000636603.1	c.-131-1815T>G		intron_variant	Intron 1 of 9	5		ENSP00000490513.1
CHRNA7	ENST00000637183.1	c.-43+50889T>G		intron_variant	Intron 1 of 8	5		ENSP00000490365.1
CHRNA7	ENST00000638106.1	c.-378-1815T>G		intron_variant	Intron 1 of 8	5		ENSP00000490413.1
CHRNA7	ENST00000635978.1	c.-42-72220T>G		intron_variant	Intron 1 of 6	5		ENSP00000490778.1

Frequencies

GnomAD3 genomes AF: 0.0588 AC: 8940 AN: 152130 Hom.: 331 Cov.: 32

Gnomad AFR AF: 0.0538

Gnomad AMI AF: 0.0527

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0508

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.0225

Gnomad FIN AF: 0.0279

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0504

Gnomad OTH AF: 0.0714

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

GnomAD4 genome AF: 0.0589 AC: 8961 AN: 152248 Hom.: 333 Cov.: 32 AF XY: 0.0590 AC XY: 4395 AN XY: 74442

African (AFR) AF: 0.0538 AC: 2235 AN: 41546

American (AMR) AF: 0.120 AC: 1833 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0508 AC: 176 AN: 3464

East Asian (EAS) AF: 0.131 AC: 675 AN: 5164

South Asian (SAS) AF: 0.0226 AC: 109 AN: 4830

European-Finnish (FIN) AF: 0.0279 AC: 296 AN: 10622

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0504 AC: 3426 AN: 68018

Other (OTH) AF: 0.0706 AC: 149 AN: 2110

Alfa AF: 0.0574 Hom.: 62

Bravo AF: 0.0651

Asia WGS AF: 0.0770 AC: 270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.43
PhyloP100		-0.029

Splicing

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

Other links and lift over

dbSNP: rs6494165; hg19: chr15-32321286;