16-89282720-G-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_013275.6(ANKRD11):​c.3822C>T​(p.Ala1274Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.039 in 1,613,692 control chromosomes in the GnomAD database, including 1,594 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 150 hom., cov: 32)
Exomes 𝑓: 0.040 ( 1444 hom. )

Consequence

ANKRD11
NM_013275.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -4.71

Publications

6 publications found
Variant links:
Genes affected
ANKRD11 (HGNC:21316): (ankyrin repeat domain containing 11) This locus encodes an ankryin repeat domain-containing protein. The encoded protein inhibits ligand-dependent activation of transcription. Mutations in this gene have been associated with KBG syndrome, which is characterized by macrodontia, distinctive craniofacial features, short stature, skeletal anomalies, global developmental delay, seizures and intellectual disability. Alternatively spliced transcript variants have been described. Related pseudogenes exist on chromosomes 2 and X. [provided by RefSeq, Jan 2012]
ANKRD11 Gene-Disease associations (from GenCC):
  • KBG syndrome
    Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P, Illumina, ClinGen
  • congenital heart defects, multiple types
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 16-89282720-G-A is Benign according to our data. Variant chr16-89282720-G-A is described in CliVar as Benign. Clinvar id is 380366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89282720-G-A is described in CliVar as Benign. Clinvar id is 380366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89282720-G-A is described in CliVar as Benign. Clinvar id is 380366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89282720-G-A is described in CliVar as Benign. Clinvar id is 380366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89282720-G-A is described in CliVar as Benign. Clinvar id is 380366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89282720-G-A is described in CliVar as Benign. Clinvar id is 380366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89282720-G-A is described in CliVar as Benign. Clinvar id is 380366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89282720-G-A is described in CliVar as Benign. Clinvar id is 380366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-4.71 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0581 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANKRD11NM_013275.6 linkc.3822C>T p.Ala1274Ala synonymous_variant Exon 9 of 13 ENST00000301030.10 NP_037407.4 Q6UB99
ANKRD11NM_001256182.2 linkc.3822C>T p.Ala1274Ala synonymous_variant Exon 10 of 14 NP_001243111.1 Q6UB99
ANKRD11NM_001256183.2 linkc.3822C>T p.Ala1274Ala synonymous_variant Exon 9 of 13 NP_001243112.1 Q6UB99

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANKRD11ENST00000301030.10 linkc.3822C>T p.Ala1274Ala synonymous_variant Exon 9 of 13 5 NM_013275.6 ENSP00000301030.4 Q6UB99

Frequencies

GnomAD3 genomes
AF:
0.0337
AC:
5116
AN:
151870
Hom.:
150
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00733
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.0245
Gnomad ASJ
AF:
0.00980
Gnomad EAS
AF:
0.0634
Gnomad SAS
AF:
0.0154
Gnomad FIN
AF:
0.129
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0380
Gnomad OTH
AF:
0.0254
GnomAD2 exomes
AF:
0.0400
AC:
10054
AN:
251352
AF XY:
0.0392
show subpopulations
Gnomad AFR exome
AF:
0.00739
Gnomad AMR exome
AF:
0.0285
Gnomad ASJ exome
AF:
0.0103
Gnomad EAS exome
AF:
0.0664
Gnomad FIN exome
AF:
0.126
Gnomad NFE exome
AF:
0.0382
Gnomad OTH exome
AF:
0.0427
GnomAD4 exome
AF:
0.0396
AC:
57821
AN:
1461704
Hom.:
1444
Cov.:
37
AF XY:
0.0385
AC XY:
28025
AN XY:
727164
show subpopulations
African (AFR)
AF:
0.00624
AC:
209
AN:
33480
American (AMR)
AF:
0.0292
AC:
1308
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.0113
AC:
295
AN:
26136
East Asian (EAS)
AF:
0.0624
AC:
2479
AN:
39700
South Asian (SAS)
AF:
0.0115
AC:
996
AN:
86254
European-Finnish (FIN)
AF:
0.122
AC:
6470
AN:
53244
Middle Eastern (MID)
AF:
0.00729
AC:
42
AN:
5764
European-Non Finnish (NFE)
AF:
0.0395
AC:
43904
AN:
1112008
Other (OTH)
AF:
0.0351
AC:
2118
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.478
Heterozygous variant carriers
0
3460
6920
10379
13839
17299
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
1684
3368
5052
6736
8420
<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:
0.0337
AC:
5117
AN:
151988
Hom.:
150
Cov.:
32
AF XY:
0.0374
AC XY:
2781
AN XY:
74280
show subpopulations
African (AFR)
AF:
0.00731
AC:
303
AN:
41438
American (AMR)
AF:
0.0244
AC:
373
AN:
15274
Ashkenazi Jewish (ASJ)
AF:
0.00980
AC:
34
AN:
3468
East Asian (EAS)
AF:
0.0637
AC:
329
AN:
5162
South Asian (SAS)
AF:
0.0156
AC:
75
AN:
4812
European-Finnish (FIN)
AF:
0.129
AC:
1361
AN:
10528
Middle Eastern (MID)
AF:
0.00340
AC:
1
AN:
294
European-Non Finnish (NFE)
AF:
0.0381
AC:
2587
AN:
67988
Other (OTH)
AF:
0.0251
AC:
53
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
243
487
730
974
1217
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
60
120
180
240
300
<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:
0.0281
Hom.:
57
Bravo
AF:
0.0251
Asia WGS
AF:
0.0400
AC:
140
AN:
3478
EpiCase
AF:
0.0307
EpiControl
AF:
0.0293

ClinVar

Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Feb 16, 2024
Athena Diagnostics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Sep 22, 2015
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

KBG syndrome Benign:2
Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Dec 05, 2021
Genome-Nilou Lab
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Inborn genetic diseases Benign:1
Apr 19, 2016
Ambry Genetics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
0.053
DANN
Benign
0.40
PhyloP100
-4.7
RBP_binding_hub_radar
1.1
RBP_regulation_power_radar
2.2
Mutation Taster
=94/6
polymorphism (auto)

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: rs61741725; hg19: chr16-89349128; COSMIC: COSV56357482; COSMIC: COSV56357482; API