rs10707844

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

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.206

Publications

1 publications found
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]
TTR Gene-Disease associations (from GenCC):
  • amyloidosis, hereditary systemic 1
    Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
  • familial amyloid neuropathy
    Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • hereditary ATTR amyloidosis
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • heart conduction disease
    Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
  • ATTRV122I amyloidosis
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

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

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TTRNM_000371.4 linkc.336+1430_336+1432delAAA intron_variant Intron 3 of 3 ENST00000237014.8 NP_000362.1 P02766E9KL36
LOC124904277XR_007066326.1 linkn.129-981_129-979delTTT intron_variant Intron 1 of 1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TTRENST00000237014.8 linkc.336+1419_336+1421delAAA intron_variant Intron 3 of 3 1 NM_000371.4 ENSP00000237014.4 P02766
TTRENST00000649620.1 linkc.336+1419_336+1421delAAA intron_variant Intron 5 of 5 ENSP00000497927.1 P02766
TTRENST00000610404.5 linkc.240+1419_240+1421delAAA intron_variant Intron 3 of 3 5 ENSP00000477599.2 A0A087WT59
ENSG00000294516ENST00000724044.1 linkn.286-981_286-979delTTT intron_variant Intron 2 of 2

Frequencies

GnomAD3 genomes
AF:
0.000131
AC:
19
AN:
144866
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.000406
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000109
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000152
Gnomad OTH
AF:
0.000502
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.000131
AC:
19
AN:
144866
Hom.:
0
Cov.:
0
AF XY:
0.000171
AC XY:
12
AN XY:
70242
show subpopulations
African (AFR)
AF:
0.000406
AC:
16
AN:
39380
American (AMR)
AF:
0.00
AC:
0
AN:
14424
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3410
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4926
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4454
European-Finnish (FIN)
AF:
0.000109
AC:
1
AN:
9160
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
298
European-Non Finnish (NFE)
AF:
0.0000152
AC:
1
AN:
65940
Other (OTH)
AF:
0.000502
AC:
1
AN:
1992
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.486
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00
Hom.:
296

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
-0.21

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs10707844; hg19: chr18-29176636; API