18-31592074-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000371.4(TTR):​c.69+103A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0158 in 1,121,304 control chromosomes in the GnomAD database, including 856 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 0.021 ( 108 hom., cov: 33)
Exomes 𝑓: 0.015 ( 748 hom. )

Consequence

TTR
NM_000371.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0250
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]

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=-0.79).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TTRNM_000371.4 linkuse as main transcriptc.69+103A>G intron_variant ENST00000237014.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TTRENST00000237014.8 linkuse as main transcriptc.69+103A>G intron_variant 1 NM_000371.4 P1

Frequencies

GnomAD3 genomes
AF:
0.0208
AC:
3164
AN:
152166
Hom.:
108
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0367
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0558
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.0270
Gnomad SAS
AF:
0.117
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000676
Gnomad OTH
AF:
0.0177
GnomAD4 exome
AF:
0.0150
AC:
14500
AN:
969020
Hom.:
748
AF XY:
0.0179
AC XY:
8996
AN XY:
502868
show subpopulations
Gnomad4 AFR exome
AF:
0.0358
Gnomad4 AMR exome
AF:
0.0733
Gnomad4 ASJ exome
AF:
0.000744
Gnomad4 EAS exome
AF:
0.0298
Gnomad4 SAS exome
AF:
0.110
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000481
Gnomad4 OTH exome
AF:
0.0162
GnomAD4 genome
AF:
0.0209
AC:
3180
AN:
152284
Hom.:
108
Cov.:
33
AF XY:
0.0226
AC XY:
1682
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.0369
Gnomad4 AMR
AF:
0.0559
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.0268
Gnomad4 SAS
AF:
0.117
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000676
Gnomad4 OTH
AF:
0.0189
Alfa
AF:
0.0108
Hom.:
3
Bravo
AF:
0.0243
Asia WGS
AF:
0.109
AC:
382
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
9.1
DANN
Benign
0.83

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs9304103; hg19: chr18-29172037; API