18-31596673-TAAA-TA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000371.4(TTR):​c.336+1431_336+1432delAA 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 0.031 ( 134 hom., cov: 0)

Consequence

TTR
NM_000371.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.74
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0779 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TTRNM_000371.4 linkuse as main transcriptc.336+1431_336+1432delAA intron_variant ENST00000237014.8 NP_000362.1 P02766E9KL36
LOC124904277XR_007066326.1 linkuse as main transcriptn.129-980_129-979delTT intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TTRENST00000237014.8 linkuse as main transcriptc.336+1431_336+1432delAA intron_variant 1 NM_000371.4 ENSP00000237014.4 P02766
TTRENST00000649620.1 linkuse as main transcriptc.336+1431_336+1432delAA intron_variant ENSP00000497927.1 P02766
TTRENST00000610404.5 linkuse as main transcriptc.240+1431_240+1432delAA intron_variant 5 ENSP00000477599.2 A0A087WT59

Frequencies

GnomAD3 genomes
AF:
0.0308
AC:
4452
AN:
144734
Hom.:
133
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.0800
Gnomad AMI
AF:
0.0125
Gnomad AMR
AF:
0.0243
Gnomad ASJ
AF:
0.0144
Gnomad EAS
AF:
0.00853
Gnomad SAS
AF:
0.00427
Gnomad FIN
AF:
0.00560
Gnomad MID
AF:
0.0236
Gnomad NFE
AF:
0.0111
Gnomad OTH
AF:
0.0226
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0309
AC:
4468
AN:
144806
Hom.:
134
Cov.:
0
AF XY:
0.0300
AC XY:
2105
AN XY:
70256
show subpopulations
Gnomad4 AFR
AF:
0.0802
Gnomad4 AMR
AF:
0.0242
Gnomad4 ASJ
AF:
0.0144
Gnomad4 EAS
AF:
0.00855
Gnomad4 SAS
AF:
0.00406
Gnomad4 FIN
AF:
0.00560
Gnomad4 NFE
AF:
0.0111
Gnomad4 OTH
AF:
0.0224

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs10707844; hg19: chr18-29176636; API