16-89281670-C-T
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_013275.6(ANKRD11):c.4872G>A(p.Ala1624=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00685 in 1,614,162 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0042 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0071 ( 46 hom. )
Consequence
ANKRD11
NM_013275.6 synonymous
NM_013275.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.11
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 16-89281670-C-T is Benign according to our data. Variant chr16-89281670-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 446826.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89281670-C-T is described in Lovd as [Benign]. Variant chr16-89281670-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-2.11 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00423 (645/152306) while in subpopulation NFE AF= 0.00723 (492/68026). AF 95% confidence interval is 0.0067. There are 0 homozygotes in gnomad4. There are 296 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 645 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ANKRD11 | NM_013275.6 | c.4872G>A | p.Ala1624= | synonymous_variant | 9/13 | ENST00000301030.10 | NP_037407.4 | |
ANKRD11 | NM_001256182.2 | c.4872G>A | p.Ala1624= | synonymous_variant | 10/14 | NP_001243111.1 | ||
ANKRD11 | NM_001256183.2 | c.4872G>A | p.Ala1624= | synonymous_variant | 9/13 | NP_001243112.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ANKRD11 | ENST00000301030.10 | c.4872G>A | p.Ala1624= | synonymous_variant | 9/13 | 5 | NM_013275.6 | ENSP00000301030 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00424 AC: 646AN: 152188Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00457 AC: 1148AN: 251206Hom.: 5 AF XY: 0.00465 AC XY: 631AN XY: 135796
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GnomAD4 exome AF: 0.00713 AC: 10420AN: 1461856Hom.: 46 Cov.: 35 AF XY: 0.00689 AC XY: 5008AN XY: 727230
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GnomAD4 genome AF: 0.00423 AC: 645AN: 152306Hom.: 0 Cov.: 32 AF XY: 0.00398 AC XY: 296AN XY: 74464
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 27, 2018 | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2024 | ANKRD11: BP4, BP7, BS2 - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 22, 2017 | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
KBG syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 30, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 27, 2016 | This alteration is classified as likely 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. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at