chr10-90920226-G-C
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_014391.3(ANKRD1):āc.150C>Gā(p.Ala50=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000646 in 1,613,974 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00035 ( 0 hom., cov: 32)
Exomes š: 0.00068 ( 13 hom. )
Consequence
ANKRD1
NM_014391.3 synonymous
NM_014391.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.331
Genes affected
ANKRD1 (HGNC:15819): (ankyrin repeat domain 1) The protein encoded by this gene is localized to the nucleus of endothelial cells and is induced by IL-1 and TNF-alpha stimulation. Studies in rat cardiomyocytes suggest that this gene functions as a transcription factor. Interactions between this protein and the sarcomeric proteins myopalladin and titin suggest that it may also be involved in the myofibrillar stretch-sensor system. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 10-90920226-G-C is Benign according to our data. Variant chr10-90920226-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 178005.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-90920226-G-C is described in Lovd as [Benign]. Variant chr10-90920226-G-C is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-0.331 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 13 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANKRD1 | NM_014391.3 | c.150C>G | p.Ala50= | synonymous_variant | 2/9 | ENST00000371697.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANKRD1 | ENST00000371697.4 | c.150C>G | p.Ala50= | synonymous_variant | 2/9 | 1 | NM_014391.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000355 AC: 54AN: 152058Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00146 AC: 366AN: 251304Hom.: 7 AF XY: 0.00202 AC XY: 275AN XY: 135810
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GnomAD4 exome AF: 0.000677 AC: 989AN: 1461798Hom.: 13 Cov.: 32 AF XY: 0.000997 AC XY: 725AN XY: 727198
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GnomAD4 genome AF: 0.000355 AC: 54AN: 152176Hom.: 0 Cov.: 32 AF XY: 0.000524 AC XY: 39AN XY: 74378
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 19, 2012 | Ala50Ala in exon 2 of ANKRD1: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 1/3738 African Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs147484763). - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 04, 2016 | 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. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2022 | ANKRD1: BP4, BP7, BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 02, 2017 | Variant summary: The ANKRD1 c.150C>G (p.Ala50Ala) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. Mutation taster predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant creates binding site for SF2/ASF and SC35. However, these predictions have yet to be confirmed by functional studies. This variant was found in 206/121400 control chromosomes (5 homozygotes) from ExAC, predominantly observed in the South Asian subpopulation at a frequency of 0.012112 (200/16512). This frequency is about 352 times the estimated maximal expected allele frequency of a pathogenic ANKRD1 variant (0.0000344), suggesting this is likely a benign polymorphism found primarily in the populations of South Asian origin. In addition, multiple clinical diagnostic laboratories in ClinVar have classified this variant as likely benign/benign. To our knowledge, this variant has not been reported in affected individuals via publications. Taken together, this variant is classified as benign. - |
Congenital total pulmonary venous return anomaly Benign:1
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
ANKRD1-related dilated cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 25, 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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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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