GeneBe

ENST00000644049.1:c.358+4013A>C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM2BP4_StrongBS1

The ENST00000644049.1(ANO4):​c.358+4013A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,220 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 ( 0 hom., cov: 32)

Consequence

ANO4
ENST00000644049.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0930

Publications

2 publications found
Variant links:
Genes affected
ANO4 (HGNC:23837): (anoctamin 4) Enables intracellular calcium activated chloride channel activity. Involved in chloride transport. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
ANO4 Gene-Disease associations (from GenCC):
  • complex neurodevelopmental disorder
    Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BS1
Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0000197 (3/152220) while in subpopulation SAS AF = 0.000414 (2/4826). AF 95% confidence interval is 0.0000729. There are 0 homozygotes in GnomAd4. There are 3 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANO4XM_011537911.3 linkc.451+4013A>C intron_variant Intron 3 of 29 XP_011536213.2 A0A2R8Y532
ANO4XM_011537912.3 linkc.451+4013A>C intron_variant Intron 3 of 29 XP_011536214.2 A0A2R8Y532
ANO4XM_011537913.3 linkc.451+4013A>C intron_variant Intron 3 of 28 XP_011536215.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANO4ENST00000644049.1 linkc.358+4013A>C intron_variant Intron 3 of 29 ENSP00000494481.1 A0A2R8Y532
ANO4ENST00000549155.6 linkn.358+4013A>C intron_variant Intron 3 of 10 2 ENSP00000449116.2 F8VW62

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152102
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152220
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74416
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41538
American (AMR)
AF:
0.00
AC:
0
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5176
South Asian (SAS)
AF:
0.000414
AC:
2
AN:
4826
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10598
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
68012
Other (OTH)
AF:
0.00
AC:
0
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.442
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
1.3
DANN
Benign
0.68
PhyloP100
-0.093

Splicing

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

Publications

Other links and lift over

dbSNP: rs10507117; hg19: chr12-101137896; API