rs3794884
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_000371.4(TTR):c.337-1560T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,018 control chromosomes in the GnomAD database, including 8,747 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.34 ( 8745 hom., cov: 31)
Exomes 𝑓: 0.45 ( 2 hom. )
Consequence
TTR
NM_000371.4 intron
NM_000371.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.258
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTR | NM_000371.4 | c.337-1560T>G | intron_variant | ENST00000237014.8 | |||
LOC124904277 | XR_007066326.1 | n.129-1313A>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTR | ENST00000237014.8 | c.337-1560T>G | intron_variant | 1 | NM_000371.4 | P1 | |||
TTR | ENST00000610404.5 | c.241-1560T>G | intron_variant | 5 | |||||
TTR | ENST00000649620.1 | c.337-1560T>G | intron_variant | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.336 AC: 51000AN: 151878Hom.: 8732 Cov.: 31
GnomAD3 genomes
?
AF:
AC:
51000
AN:
151878
Hom.:
Cov.:
31
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:
GnomAD4 exome AF: 0.455 AC: 10AN: 22Hom.: 2 AF XY: 0.563 AC XY: 9AN XY: 16
GnomAD4 exome
AF:
AC:
10
AN:
22
Hom.:
AF XY:
AC XY:
9
AN XY:
16
Gnomad4 NFE exome
AF:
GnomAD4 genome ? AF: 0.336 AC: 51055AN: 151996Hom.: 8745 Cov.: 31 AF XY: 0.332 AC XY: 24630AN XY: 74298
GnomAD4 genome
?
AF:
AC:
51055
AN:
151996
Hom.:
Cov.:
31
AF XY:
AC XY:
24630
AN XY:
74298
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
928
AN:
3478
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at