chr18-31596673-T-TA

Position:

• chr18-31596673-T-TA

Variant summary

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

The NM_000371.4(TTR):​c.336+1432dupA 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 (72 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 (AFR) allele frequency at 95% confidence interval = 0.0588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTR	NM_000371.4	c.336+1432dupA		intron_variant		ENST00000237014.8	NP_000362.1
LOC124904277	XR_007066326.1	n.129-979dupT		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTR	ENST00000237014.8	c.336+1432dupA		intron_variant		1	NM_000371.4	ENSP00000237014.4
TTR	ENST00000649620.1	c.336+1432dupA		intron_variant				ENSP00000497927.1
TTR	ENST00000610404.5	c.240+1432dupA		intron_variant		5		ENSP00000477599.2

Frequencies

GnomAD3 genomes AF: 0.0189 AC: 2743 AN: 144816 Hom.: 73 Cov.: 0

Gnomad AFR AF: 0.0608

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00763

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00122

Gnomad SAS AF: 0.0157

Gnomad FIN AF: 0.00131

Gnomad MID AF: 0.0101

Gnomad NFE AF: 0.00174

Gnomad OTH AF: 0.0166

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

GnomAD4 genome AF: 0.0190 AC: 2747 AN: 144880 Hom.: 72 Cov.: 0 AF XY: 0.0184 AC XY: 1290 AN XY: 70290

Gnomad4 AFR AF: 0.0608

Gnomad4 AMR AF: 0.00755

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00122

Gnomad4 SAS AF: 0.0156

Gnomad4 FIN AF: 0.00131

Gnomad4 NFE AF: 0.00174

Gnomad4 OTH AF: 0.0169

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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;