rs10707844
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BS2_Supporting
The NM_000371.4(TTR):c.336+1430_336+1432delAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.00013 ( 0 hom., cov: 0)
Consequence
TTR
NM_000371.4 intron
NM_000371.4 intron
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.206
Publications
1 publications found
Genes affected
TTR (HGNC:12405): (transthyretin) This gene encodes one of the three prealbumins, which include alpha-1-antitrypsin, transthyretin and orosomucoid. The encoded protein, transthyretin, is a homo-tetrameric carrier protein, which transports thyroid hormones in the plasma and cerebrospinal fluid. It is also involved in the transport of retinol (vitamin A) in the plasma by associating with retinol-binding protein. The protein may also be involved in other intracellular processes including proteolysis, nerve regeneration, autophagy and glucose homeostasis. Mutations in this gene are associated with amyloid deposition, predominantly affecting peripheral nerves or the heart, while a small percentage of the gene mutations are non-amyloidogenic. The mutations are implicated in the etiology of several diseases, including amyloidotic polyneuropathy, euthyroid hyperthyroxinaemia, amyloidotic vitreous opacities, cardiomyopathy, oculoleptomeningeal amyloidosis, meningocerebrovascular amyloidosis and carpal tunnel syndrome. [provided by RefSeq, Aug 2017]
TTR Gene-Disease associations (from GenCC):
- amyloidosis, hereditary systemic 1Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
- familial amyloid neuropathyInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- hereditary ATTR amyloidosisInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- heart conduction diseaseInheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
- ATTRV122I amyloidosisInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -1 ACMG points.
BS2
High AC in GnomAd4 at 19 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTR | ENST00000237014.8 | c.336+1419_336+1421delAAA | intron_variant | Intron 3 of 3 | 1 | NM_000371.4 | ENSP00000237014.4 | |||
TTR | ENST00000649620.1 | c.336+1419_336+1421delAAA | intron_variant | Intron 5 of 5 | ENSP00000497927.1 | |||||
TTR | ENST00000610404.5 | c.240+1419_240+1421delAAA | intron_variant | Intron 3 of 3 | 5 | ENSP00000477599.2 | ||||
ENSG00000294516 | ENST00000724044.1 | n.286-981_286-979delTTT | intron_variant | Intron 2 of 2 |
Frequencies
GnomAD3 genomes AF: 0.000131 AC: 19AN: 144866Hom.: 0 Cov.: 0 show subpopulations
GnomAD3 genomes
AF:
AC:
19
AN:
144866
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Cov.:
0
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome AF: 0.000131 AC: 19AN: 144866Hom.: 0 Cov.: 0 AF XY: 0.000171 AC XY: 12AN XY: 70242 show subpopulations
GnomAD4 genome
AF:
AC:
19
AN:
144866
Hom.:
Cov.:
0
AF XY:
AC XY:
12
AN XY:
70242
show subpopulations
African (AFR)
AF:
AC:
16
AN:
39380
American (AMR)
AF:
AC:
0
AN:
14424
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3410
East Asian (EAS)
AF:
AC:
0
AN:
4926
South Asian (SAS)
AF:
AC:
0
AN:
4454
European-Finnish (FIN)
AF:
AC:
1
AN:
9160
Middle Eastern (MID)
AF:
AC:
0
AN:
298
European-Non Finnish (NFE)
AF:
AC:
1
AN:
65940
Other (OTH)
AF:
AC:
1
AN:
1992
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.486
Heterozygous variant carriers
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Allele balance
Alfa
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ClinVar
Not reported inComputational scores
Source:
Name
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Prediction
PhyloP100
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
Publications
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