20-63346719-G-A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000744.7(CHRNA4):​c.*19C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 1,599,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

CHRNA4
NM_000744.7 3_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.22

Publications

0 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: Labcorp Genetics (formerly Invitae), G2P
  • 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
Variant 20-63346719-G-A is Benign according to our data. Variant chr20-63346719-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1283389.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHRNA4NM_000744.7 linkc.*19C>T 3_prime_UTR_variant Exon 6 of 6 ENST00000370263.9 NP_000735.1 P43681-1B4DK78Q59FV0
CHRNA4NR_046317.2 linkn.2112C>T non_coding_transcript_exon_variant Exon 6 of 6
CHRNA4NM_001256573.2 linkc.*19C>T 3_prime_UTR_variant Exon 6 of 6 NP_001243502.1 P43681Q4VAQ3B4DK78Q59FV0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHRNA4ENST00000370263.9 linkc.*19C>T 3_prime_UTR_variant Exon 6 of 6 1 NM_000744.7 ENSP00000359285.4 P43681-1

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152230
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000264
AC:
6
AN:
227152
AF XY:
0.0000321
show subpopulations
Gnomad AFR exome
AF:
0.000138
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000580
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000985
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000117
AC:
17
AN:
1447674
Hom.:
0
Cov.:
32
AF XY:
0.0000153
AC XY:
11
AN XY:
720100
show subpopulations
African (AFR)
AF:
0.0000601
AC:
2
AN:
33300
American (AMR)
AF:
0.00
AC:
0
AN:
43522
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26000
East Asian (EAS)
AF:
0.0000509
AC:
2
AN:
39330
South Asian (SAS)
AF:
0.0000233
AC:
2
AN:
85666
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
45358
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5720
European-Non Finnish (NFE)
AF:
0.00000812
AC:
9
AN:
1108718
Other (OTH)
AF:
0.0000333
AC:
2
AN:
60060
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.493
Heterozygous variant carriers
0
1
3
4
6
7
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.0000328
AC:
5
AN:
152230
Hom.:
0
Cov.:
33
AF XY:
0.0000672
AC XY:
5
AN XY:
74366
show subpopulations
African (AFR)
AF:
0.0000724
AC:
3
AN:
41464
American (AMR)
AF:
0.00
AC:
0
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5192
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10620
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000294
AC:
2
AN:
68040
Other (OTH)
AF:
0.00
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.495
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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.:
0
Bravo
AF:
0.0000264
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Feb 01, 2017
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.40
DANN
Benign
0.49
PhyloP100
-1.2

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

Other links and lift over

dbSNP: rs770936281; hg19: chr20-61978071; COSMIC: COSV100937483; COSMIC: COSV100937483; API