rs755176025
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Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7
The NM_000037.4(ANK1):c.1686G>A(p.Pro562Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,614,058 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 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
ANK1
NM_000037.4 synonymous
NM_000037.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.42
Genes affected
ANK1 (HGNC:492): (ankyrin 1) Ankyrins are a family of proteins that link the integral membrane proteins to the underlying spectrin-actin cytoskeleton and play key roles in activities such as cell motility, activation, proliferation, contact and the maintenance of specialized membrane domains. Multiple isoforms of ankyrin with different affinities for various target proteins are expressed in a tissue-specific, developmentally regulated manner. Most ankyrins are typically composed of three structural domains: an amino-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain; and a carboxy-terminal regulatory domain which is the least conserved and subject to variation. Ankyrin 1, the prototype of this family, was first discovered in the erythrocytes, but since has also been found in brain and muscles. Mutations in erythrocytic ankyrin 1 have been associated in approximately half of all patients with hereditary spherocytosis. Complex patterns of alternative splicing in the regulatory domain, giving rise to different isoforms of ankyrin 1 have been described. Truncated muscle-specific isoforms of ankyrin 1 resulting from usage of an alternate promoter have also been identified. [provided by RefSeq, Dec 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant 8-41714991-C-T is Benign according to our data. Variant chr8-41714991-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 261293.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-3.42 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ANK1 | NM_000037.4 | c.1686G>A | p.Pro562Pro | synonymous_variant | 15/43 | ENST00000289734.13 | NP_000028.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ANK1 | ENST00000289734.13 | c.1686G>A | p.Pro562Pro | synonymous_variant | 15/43 | 1 | NM_000037.4 | ENSP00000289734.8 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152208Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251224Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135788
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461850Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727226
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152208Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74370
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at