18-31591160-A-T
Variant names:
Variant summary
Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBS2_Supporting
The ENST00000649620.1(TTR):c.-1-742A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00432 in 145,960 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0043 ( 8 hom., cov: 29)
Consequence
TTR
ENST00000649620.1 intron
ENST00000649620.1 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0740
Publications
2 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
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -13 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
Variant 18-31591160-A-T is Benign according to our data. Variant chr18-31591160-A-T is described in CliVar as Benign/Likely_benign. Clinvar id is 744399.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-31591160-A-T is described in CliVar as Benign/Likely_benign. Clinvar id is 744399.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-31591160-A-T is described in CliVar as Benign/Likely_benign. Clinvar id is 744399.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-31591160-A-T is described in CliVar as Benign/Likely_benign. Clinvar id is 744399.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-31591160-A-T is described in CliVar as Benign/Likely_benign. Clinvar id is 744399.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-31591160-A-T is described in CliVar as Benign/Likely_benign. Clinvar id is 744399.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-31591160-A-T is described in CliVar as Benign/Likely_benign. Clinvar id is 744399.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomAd4 at 630 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTR | ENST00000649620.1 | c.-1-742A>T | intron_variant | Intron 2 of 5 | ENSP00000497927.1 | |||||
TTR | ENST00000610404.5 | c.-27-1736A>T | intron_variant | Intron 1 of 3 | 5 | ENSP00000477599.2 | ||||
TTR | ENST00000613781.2 | c.-1-742A>T | intron_variant | Intron 1 of 1 | 5 | ENSP00000479174.2 | ||||
TTR | ENST00000676075.1 | c.-1-742A>T | intron_variant | Intron 1 of 1 | ENSP00000502027.1 |
Frequencies
GnomAD3 genomes AF: 0.00430 AC: 628AN: 145884Hom.: 8 Cov.: 29 show subpopulations
GnomAD3 genomes
AF:
AC:
628
AN:
145884
Hom.:
Cov.:
29
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome AF: 0.00432 AC: 630AN: 145960Hom.: 8 Cov.: 29 AF XY: 0.00465 AC XY: 329AN XY: 70722 show subpopulations
GnomAD4 genome
AF:
AC:
630
AN:
145960
Hom.:
Cov.:
29
AF XY:
AC XY:
329
AN XY:
70722
show subpopulations
African (AFR)
AF:
AC:
50
AN:
39134
American (AMR)
AF:
AC:
108
AN:
14630
Ashkenazi Jewish (ASJ)
AF:
AC:
2
AN:
3434
East Asian (EAS)
AF:
AC:
89
AN:
4994
South Asian (SAS)
AF:
AC:
80
AN:
4672
European-Finnish (FIN)
AF:
AC:
30
AN:
9156
Middle Eastern (MID)
AF:
AC:
2
AN:
274
European-Non Finnish (NFE)
AF:
AC:
256
AN:
66772
Other (OTH)
AF:
AC:
8
AN:
1994
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.461
Heterozygous variant carriers
0
26
52
79
105
131
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
10
20
30
40
50
<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:
Hom.:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hyperthyroxinemia, dystransthyretinemic;C2751492:Amyloidosis, hereditary systemic 1;C5779776:Carpal tunnel syndrome 1 Benign:1
Oct 27, 2021
Fulgent Genetics, Fulgent Genetics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Amyloidosis, hereditary systemic 1 Benign:1
Jan 20, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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