15-32030549-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000746.6(CHRNA7):c.-46G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00438 in 1,442,078 control chromosomes in the GnomAD database, including 239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 139 hom., cov: 31)

Exomes 𝑓: 0.0022 ( 100 hom. )

Consequence

CHRNA7
NM_000746.6 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0270

Publications

3 publications found

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]

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

CHRNA7 links:

LOC124903441 (HGNC:):

LOC124903441 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 15-32030549-G-T is Benign according to our data. Variant chr15-32030549-G-T is described in ClinVar as Benign. ClinVar VariationId is 1183237.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0753 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000746.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHRNA7	NM_000746.6	MANE Select	c.-46G>T	5_prime_UTR	Exon 1 of 10	NP_000737.1	P36544-1
CHRNA7	NM_001190455.3		c.-46G>T	5_prime_UTR	Exon 1 of 10	NP_001177384.1	P36544-2
CHRNA7	NR_046324.1		n.67G>T	non_coding_transcript_exon	Exon 1 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHRNA7	ENST00000306901.9	TSL:1 MANE Select	c.-46G>T	5_prime_UTR	Exon 1 of 10	ENSP00000303727.2	P36544-1
CHRNA7	ENST00000454250.7	TSL:2	c.-46G>T	5_prime_UTR	Exon 1 of 10	ENSP00000407546.3	P36544-2
CHRNA7	ENST00000675428.1		c.-46G>T	5_prime_UTR	Exon 1 of 10	ENSP00000502560.1	P36544-2

Frequencies

GnomAD3 genomes

AF:

0.0225

AC:

3422

AN:

151864

Hom.:

139

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0776

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00917

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0230

GnomAD2 exomes

AF:

0.00223

AC:

131

AN:

58760

AF XY:

0.00186

show subpopulations

Gnomad AFR exome

AF:

0.0835

Gnomad AMR exome

AF:

0.00375

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000333

Gnomad OTH exome

AF:

0.00413

GnomAD4 exome

AF:

0.00224

AC:

2896

AN:

1290108

Hom.:

100

Cov.:

AF XY:

0.00189

AC XY:

1196

AN XY:

632902

show subpopulations

African (AFR)

AF:

0.0830

AC:

2163

AN:

26056

American (AMR)

AF:

0.00565

AC:

128

AN:

22636

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21322

East Asian (EAS)

AF:

0.00

AC:

AN:

27994

South Asian (SAS)

AF:

0.000150

AC:

AN:

66748

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32816

Middle Eastern (MID)

AF:

0.00708

AC:

AN:

3814

European-Non Finnish (NFE)

AF:

0.000239

AC:

247

AN:

1035402

Other (OTH)

AF:

0.00602

AC:

321

AN:

53320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

143

286

430

573

716

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

234

312

390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0225

AC:

3426

AN:

151970

Hom.:

139

Cov.:

AF XY:

0.0211

AC XY:

1571

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.0775

AC:

3215

AN:

41478

American (AMR)

AF:

0.00910

AC:

139

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5122

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10564

Middle Eastern (MID)

AF:

0.0103

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

67920

Other (OTH)

AF:

0.0227

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

154

309

463

618

772

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000429

Hom.:

Bravo

AF:

0.0259

Asia WGS

AF:

0.00551

AC:

AN:

3462

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

6.6

(source)

DANN

Benign

0.67

PhyloP100

-0.027

PromoterAI

0.023

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over