rs71383038

Positions:

• chr18-31590652-G-GCA
• chr18-31590652-G-GCACACACACACA
• chr18-31590652-G-GCACACACACACACACACA
• chr18-31590652-G-GCACACACA
• chr18-31590652-GCACACACA-G
• chr18-31590652-G-GCACACACACA
• chr18-31590652-GCACACA-G
• chr18-31590652-G-GCACA
• chr18-31590652-GCACA-G
• chr18-31590652-GCA-G
• chr18-31590652-G-GCACACACACACACA
• chr18-31590652-G-GCACACA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000649620.1(TTR):​c.-1-1231_-1-1230dup 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 0.019 (83 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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0593 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_-27-2224dup		intron_variant		5		ENSP00000477599
TTR	ENST00000613781.2	c.-1-1231_-1-1230dup		intron_variant		5		ENSP00000479174
TTR	ENST00000649620.1	c.-1-1231_-1-1230dup		intron_variant				ENSP00000497927	P1
TTR	ENST00000676075.1	c.-1-1231_-1-1230dup		intron_variant				ENSP00000502027

Frequencies

GnomAD3 genomes AF: 0.0193 AC: 2920 AN: 151130 Hom.: 83 Cov.: 0

Gnomad AFR AF: 0.0614

Gnomad AMI AF: 0.00333

Gnomad AMR AF: 0.00937

Gnomad ASJ AF: 0.0151

Gnomad EAS AF: 0.00427

Gnomad SAS AF: 0.00437

Gnomad FIN AF: 0.000775

Gnomad MID AF: 0.00962

Gnomad NFE AF: 0.00142

Gnomad OTH AF: 0.0175

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

GnomAD4 genome AF: 0.0193 AC: 2919 AN: 151236 Hom.: 83 Cov.: 0 AF XY: 0.0193 AC XY: 1423 AN XY: 73868

Gnomad4 AFR AF: 0.0613

Gnomad4 AMR AF: 0.00936

Gnomad4 ASJ AF: 0.0151

Gnomad4 EAS AF: 0.00428

Gnomad4 SAS AF: 0.00438

Gnomad4 FIN AF: 0.000775

Gnomad4 NFE AF: 0.00142

Gnomad4 OTH AF: 0.0173

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;