18-31596673-TAAA-TAA

Position:

• chr18-31596673-TAAA-TAA

Variant summary

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

The NM_000371.4(TTR):​c.336+1432del 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 0.38 (10259 hom., cov: 0)
• Consequence: TTR NM_000371.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05

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]

LOC124904277 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTR	NM_000371.4	c.336+1432del		intron_variant		ENST00000237014.8
LOC124904277	XR_007066326.1	n.129-979del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTR	ENST00000237014.8	c.336+1432del		intron_variant		1	NM_000371.4	P1
TTR	ENST00000610404.5	c.240+1432del		intron_variant		5
TTR	ENST00000649620.1	c.336+1432del		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 55384 AN: 144532 Hom.: 10258 Cov.: 0

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.523

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.383 AC: 55411 AN: 144600 Hom.: 10259 Cov.: 0 AF XY: 0.382 AC XY: 26773 AN XY: 70150

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.409

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs10707844; hg19: chr18-29176636;