rs3827020

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_000744.7(CHRNA4):c.1758+14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,612,344 control chromosomes in the GnomAD database, including 32,367 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3203 hom., cov: 34)

Exomes 𝑓: 0.19 ( 29164 hom. )

Consequence

CHRNA4
NM_000744.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -7.11

Publications

13 publications found

Variant links:

Genes affected

CHRNA4 (HGNC:1958): (cholinergic receptor nicotinic alpha 4 subunit) This gene encodes a nicotinic acetylcholine receptor, which belongs to a superfamily of ligand-gated ion channels that play a role in fast signal transmission at synapses. These pentameric receptors can bind acetylcholine, which causes an extensive change in conformation that leads to the opening of an ion-conducting channel across the plasma membrane. This protein is an integral membrane receptor subunit that can interact with either nAChR beta-2 or nAChR beta-4 to form a functional receptor. Mutations in this gene cause nocturnal frontal lobe epilepsy type 1. Polymorphisms in this gene that provide protection against nicotine addiction have been described. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]

CHRNA4 Gene-Disease associations (from GenCC):

autosomal dominant nocturnal frontal lobe epilepsy 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
familial sleep-related hypermotor epilepsy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
autosomal dominant nocturnal frontal lobe epilepsy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CHRNA4 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=-0.93).

BP6

Variant 20-63349639-T-C is Benign according to our data. Variant chr20-63349639-T-C is described in ClinVar as Benign. ClinVar VariationId is 93429.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000744.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHRNA4	NM_000744.7	MANE Select	c.1758+14A>G	intron	N/A	NP_000735.1	P43681-1
CHRNA4	NM_001256573.2		c.1230+14A>G	intron	N/A	NP_001243502.1	Q4VAQ3
CHRNA4	NR_046317.2		n.1967+14A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHRNA4	ENST00000370263.9	TSL:1 MANE Select	c.1758+14A>G	intron	N/A	ENSP00000359285.4	P43681-1
CHRNA4	ENST00000463705.5	TSL:1	n.2406+14A>G	intron	N/A
CHRNA4	ENST00000467563.3	TSL:1	n.1828+14A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.197

AC:

29983

AN:

152102

Hom.:

3202

Cov.:

show subpopulations

Gnomad AFR

AF:

0.176

Gnomad AMI

AF:

0.297

Gnomad AMR

AF:

0.220

Gnomad ASJ

AF:

0.148

Gnomad EAS

AF:

0.475

Gnomad SAS

AF:

0.165

Gnomad FIN

AF:

0.208

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.186

Gnomad OTH

AF:

0.198

GnomAD2 exomes

AF:

0.217

AC:

53721

AN:

247432

AF XY:

0.210

show subpopulations

Gnomad AFR exome

AF:

0.170

Gnomad AMR exome

AF:

0.299

Gnomad ASJ exome

AF:

0.147

Gnomad EAS exome

AF:

0.467

Gnomad FIN exome

AF:

0.199

Gnomad NFE exome

AF:

0.183

Gnomad OTH exome

AF:

0.194

GnomAD4 exome

AF:

0.192

AC:

280902

AN:

1460124

Hom.:

29164

Cov.:

AF XY:

0.192

AC XY:

139178

AN XY:

726396

show subpopulations

African (AFR)

AF:

0.174

AC:

5809

AN:

33466

American (AMR)

AF:

0.289

AC:

12914

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.155

AC:

4037

AN:

26122

East Asian (EAS)

AF:

0.463

AC:

18378

AN:

39688

South Asian (SAS)

AF:

0.163

AC:

14045

AN:

86254

European-Finnish (FIN)

AF:

0.200

AC:

10409

AN:

51998

Middle Eastern (MID)

AF:

0.153

AC:

880

AN:

5766

European-Non Finnish (NFE)

AF:

0.182

AC:

202702

AN:

1111748

Other (OTH)

AF:

0.194

AC:

11728

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

12488

24976

37463

49951

62439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7280

14560

21840

29120

36400

<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:

0.197

AC:

29990

AN:

152220

Hom.:

3203

Cov.:

AF XY:

0.198

AC XY:

14734

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.176

AC:

7308

AN:

41542

American (AMR)

AF:

0.220

AC:

3364

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.148

AC:

515

AN:

3472

East Asian (EAS)

AF:

0.474

AC:

2449

AN:

5168

South Asian (SAS)

AF:

0.164

AC:

791

AN:

4826

European-Finnish (FIN)

AF:

0.208

AC:

2203

AN:

10608

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.186

AC:

12626

AN:

67982

Other (OTH)

AF:

0.200

AC:

422

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1271

2543

3814

5086

6357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

330

660

990

1320

1650

<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:

0.137

Hom.:

357

Bravo

AF:

0.201

Asia WGS

AF:

0.319

AC:

1107

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autosomal dominant nocturnal frontal lobe epilepsy 1 (3)

not specified (3)

not provided (2)

Autosomal dominant nocturnal frontal lobe epilepsy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.052

(source)

DANN

Benign

0.26

PhyloP100

-7.1

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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