chr18-31590652-GCA-G

Position:

• chr18-31590652-GCA-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The ENST00000649620.1(TTR):​c.-1-1231_-1-1230del 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 0.31 (7384 hom., cov: 0)
• Consequence: TTR ENST00000649620.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 18-31590652-GCA-G is Benign according to our data. Variant chr18-31590652-GCA-G is described in Lovd as [Benign]. Variant chr18-31590652-GCA-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTR	ENST00000610404.5	c.-27-2225_-27-2224del		intron_variant		5		ENSP00000477599
TTR	ENST00000613781.2	c.-1-1231_-1-1230del		intron_variant		5		ENSP00000479174
TTR	ENST00000649620.1	c.-1-1231_-1-1230del		intron_variant				ENSP00000497927	P1
TTR	ENST00000676075.1	c.-1-1231_-1-1230del		intron_variant				ENSP00000502027

Frequencies

GnomAD3 genomes AF: 0.310 AC: 46710 AN: 150914 Hom.: 7378 Cov.: 0

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.310 AC: 46744 AN: 151016 Hom.: 7384 Cov.: 0 AF XY: 0.306 AC XY: 22556 AN XY: 73738

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.339

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.349

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;