chr18-31568851-G-A

Position:

• chr18-31568851-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000649620.1(TTR):​c.-102+11720G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 151,940 control chromosomes in the GnomAD database, including 31,519 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (31519 hom., cov: 31)
• Consequence: TTR ENST00000649620.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTR	ENST00000610404.5	c.-28+11720G>A		intron_variant		5
TTR	ENST00000649620.1	c.-102+11720G>A		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95805 AN: 151822 Hom.: 31458 Cov.: 31

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.917

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.619

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

GnomAD4 genome AF: 0.631 AC: 95932 AN: 151940 Hom.: 31519 Cov.: 31 AF XY: 0.633 AC XY: 46958 AN XY: 74240

Gnomad4 AFR AF: 0.783

Gnomad4 AMR AF: 0.697

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.918

Gnomad4 SAS AF: 0.547

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.623

Alfa AF: 0.554 Hom.: 10830

Bravo AF: 0.660

Asia WGS AF: 0.745 AC: 2591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.28
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1667234; hg19: chr18-29148814;