18-31594143-CAA-CA

Position:

• chr18-31594143-CAA-CA

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP6

The NM_000371.4(TTR):​c.201-966delA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00096 (0 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: TTR NM_000371.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.870

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• BP6: Variant 18-31594143-CA-C is Benign according to our data. Variant chr18-31594143-CA-C is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTR	NM_000371.4	c.201-966delA		intron_variant		ENST00000237014.8	NP_000362.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTR	ENST00000237014.8	c.201-966delA		intron_variant		1	NM_000371.4	ENSP00000237014.4
TTR	ENST00000649620.1	c.201-966delA		intron_variant				ENSP00000497927.1
TTR	ENST00000610404.5	c.105-966delA		intron_variant		5		ENSP00000477599.2
TTR	ENST00000541025.2	n.227-966delA		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 113 AN: 118700 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.000284

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00109

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000460

Gnomad SAS AF: 0.000780

Gnomad FIN AF: 0.00648

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000749

Gnomad OTH AF: 0.00124

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000960 AC: 114 AN: 118736 Hom.: 0 Cov.: 32 AF XY: 0.00108 AC XY: 62 AN XY: 57286

Gnomad4 AFR AF: 0.000315

Gnomad4 AMR AF: 0.00109

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000462

Gnomad4 SAS AF: 0.000783

Gnomad4 FIN AF: 0.00648

Gnomad4 NFE AF: 0.000749

Gnomad4 OTH AF: 0.00123

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs58272364; hg19: chr18-29174106;