chr18-31590652-G-GCACACACA

Position:

• chr18-31590652-G-GCACACACA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000649620.1(TTR):​c.-1-1250_-1-1249insCACACACA 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 0.011 (18 hom., cov: 0)
• Consequence: TTR ENST00000649620.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.262

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0112 (1697/151238) while in subpopulation AFR AF= 0.0396 (1641/41402). AF 95% confidence interval is 0.038. There are 18 homozygotes in gnomad4. There are 846 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1697 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.31590652_31590653insCACACACA		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTR	ENST00000649620.1	c.-1-1250_-1-1249insCACACACA		intron_variant				ENSP00000497927.1
TTR	ENST00000610404.5	c.-27-2244_-27-2243insCACACACA		intron_variant		5		ENSP00000477599.2
TTR	ENST00000613781.2	c.-1-1250_-1-1249insCACACACA		intron_variant		5		ENSP00000479174.2
TTR	ENST00000676075.1	c.-1-1250_-1-1249insCACACACA		intron_variant				ENSP00000502027.1

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1697 AN: 151132 Hom.: 18 Cov.: 0

Gnomad AFR AF: 0.0397

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00277

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000443

Gnomad OTH AF: 0.00485

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

GnomAD4 genome AF: 0.0112 AC: 1697 AN: 151238 Hom.: 18 Cov.: 0 AF XY: 0.0115 AC XY: 846 AN XY: 73868

Gnomad4 AFR AF: 0.0396

Gnomad4 AMR AF: 0.00277

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000443

Gnomad4 OTH AF: 0.00480

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3834979; hg19: chr18-29170615;