chr15-32101283-C-CT

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000746.6(CHRNA7):c.196-5dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.37 ( 9812 hom., cov: 0)

Exomes 𝑓: 0.35 ( 2312 hom. )

Failed GnomAD Quality Control

Consequence

CHRNA7
NM_000746.6 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.508

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 15-32101283-C-CT is Benign according to our data. Variant chr15-32101283-C-CT is described in ClinVar as Benign. ClinVar VariationId is 1260396.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.417 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.196-5dupT	splice_region intron	N/A	NP_000737.1	P36544-1
CHRNA7	NM_001190455.3		c.283-5dupT	splice_region intron	N/A	NP_001177384.1	P36544-2
CHRNA7	NR_046324.1		n.308-5dupT	splice_region intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHRNA7	ENST00000306901.9	TSL:1 MANE Select	c.196-5dupT	splice_region intron	N/A	ENSP00000303727.2	P36544-1
CHRNA7	ENST00000635759.1	TSL:1	n.61-5dupT	splice_region intron	N/A	ENSP00000489825.1	A0A1B0GTT0
CHRNA7	ENST00000637786.2	TSL:1	n.196-5dupT	splice_region intron	N/A	ENSP00000490015.1	A0A1B0GU93

Frequencies

GnomAD3 genomes

AF:

0.367

AC:

51788

AN:

141186

Hom.:

9805

Cov.:

show subpopulations

Gnomad AFR

AF:

0.325

Gnomad AMI

AF:

0.446

Gnomad AMR

AF:

0.338

Gnomad ASJ

AF:

0.434

Gnomad EAS

AF:

0.0954

Gnomad SAS

AF:

0.250

Gnomad FIN

AF:

0.352

Gnomad MID

AF:

0.490

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.397

GnomAD2 exomes

AF:

0.347

AC:

51230

AN:

147816

AF XY:

0.348

show subpopulations

Gnomad AFR exome

AF:

0.313

Gnomad AMR exome

AF:

0.295

Gnomad ASJ exome

AF:

0.354

Gnomad EAS exome

AF:

0.264

Gnomad FIN exome

AF:

0.374

Gnomad NFE exome

AF:

0.378

Gnomad OTH exome

AF:

0.347

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.349

AC:

444503

AN:

1273894

Hom.:

2312

Cov.:

AF XY:

0.347

AC XY:

220125

AN XY:

634480

show subpopulations

African (AFR)

AF:

0.286

AC:

7968

AN:

27870

American (AMR)

AF:

0.271

AC:

7643

AN:

28208

Ashkenazi Jewish (ASJ)

AF:

0.348

AC:

7697

AN:

22124

East Asian (EAS)

AF:

0.243

AC:

8461

AN:

34772

South Asian (SAS)

AF:

0.264

AC:

18471

AN:

69980

European-Finnish (FIN)

AF:

0.331

AC:

15185

AN:

45812

Middle Eastern (MID)

AF:

0.383

AC:

1903

AN:

4972

European-Non Finnish (NFE)

AF:

0.364

AC:

359212

AN:

987368

Other (OTH)

AF:

0.340

AC:

17963

AN:

52788

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.417

Heterozygous variant carriers

14543

29086

43628

58171

72714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13832

27664

41496

55328

69160

<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:

0.367

AC:

51794

AN:

141188

Hom.:

9812

Cov.:

AF XY:

0.359

AC XY:

24391

AN XY:

67986

show subpopulations

African (AFR)

AF:

0.325

AC:

12450

AN:

38328

American (AMR)

AF:

0.338

AC:

4806

AN:

14232

Ashkenazi Jewish (ASJ)

AF:

0.434

AC:

1471

AN:

3392

East Asian (EAS)

AF:

0.0958

AC:

465

AN:

4854

South Asian (SAS)

AF:

0.250

AC:

1104

AN:

4422

European-Finnish (FIN)

AF:

0.352

AC:

2590

AN:

7360

Middle Eastern (MID)

AF:

0.500

AC:

139

AN:

278

European-Non Finnish (NFE)

AF:

0.422

AC:

27602

AN:

65482

Other (OTH)

AF:

0.395

AC:

767

AN:

1944

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1435

2870

4304

5739

7174

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

498

996

1494

1992

2490

<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:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.51

Mutation Taster

=26/74

disease causing

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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