rs13381522

Positions:

• chr18-31589970-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000649620.1(TTR):​c.-1-1932C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,222 control chromosomes in the GnomAD database, including 2,161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency: Genomes: 𝑓 0.12 (2161 hom., cov: 33)
• Consequence: TTR ENST00000649620.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 18-31589970-C-T is Benign according to our data. Variant chr18-31589970-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 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.-27-2926C>T		intron_variant		5		ENSP00000477599
TTR	ENST00000613781.2	c.-1-1932C>T		intron_variant		5		ENSP00000479174
TTR	ENST00000649620.1	c.-1-1932C>T		intron_variant				ENSP00000497927	P1
TTR	ENST00000676075.1	c.-1-1932C>T		intron_variant				ENSP00000502027

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18558 AN: 152104 Hom.: 2149 Cov.: 33

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0498

Gnomad EAS AF: 0.0748

Gnomad SAS AF: 0.0391

Gnomad FIN AF: 0.0255

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0400

Gnomad OTH AF: 0.0975

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

GnomAD4 genome AF: 0.122 AC: 18614 AN: 152222 Hom.: 2161 Cov.: 33 AF XY: 0.121 AC XY: 8982 AN XY: 74430

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.0498

Gnomad4 EAS AF: 0.0750

Gnomad4 SAS AF: 0.0390

Gnomad4 FIN AF: 0.0255

Gnomad4 NFE AF: 0.0400

Gnomad4 OTH AF: 0.0965

Alfa AF: 0.122 Hom.: 336

Bravo AF: 0.140

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.3
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13381522; hg19: chr18-29169933;