rs853308

Positions:

• chr8-132917672-C-T

Variant summary

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

The NM_003235.5(TG):​c.4379-1704C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 151,532 control chromosomes in the GnomAD database, including 15,659 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 0.41 (15659 hom., cov: 28)
• Consequence: TG NM_003235.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.448

Genes affected

TG (HGNC:11764): (thyroglobulin) Thyroglobulin (Tg) is a glycoprotein homodimer produced predominantly by the thryroid gland. It acts as a substrate for the synthesis of thyroxine and triiodothyronine as well as the storage of the inactive forms of thyroid hormone and iodine. Thyroglobulin is secreted from the endoplasmic reticulum to its site of iodination, and subsequent thyroxine biosynthesis, in the follicular lumen. Mutations in this gene cause thyroid dyshormonogenesis, manifested as goiter, and are associated with moderate to severe congenital hypothyroidism. Polymorphisms in this gene are associated with susceptibility to autoimmune thyroid diseases (AITD) such as Graves disease and Hashimoto thryoiditis. [provided by RefSeq, Nov 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TG	NM_003235.5	c.4379-1704C>T		intron_variant		ENST00000220616.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TG	ENST00000220616.9	c.4379-1704C>T		intron_variant		1	NM_003235.5	P1
TG	ENST00000523756.5	c.*592-1704C>T		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62474 AN: 151414 Hom.: 15660 Cov.: 28

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.412 AC: 62474 AN: 151532 Hom.: 15659 Cov.: 28 AF XY: 0.418 AC XY: 30942 AN XY: 74004

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.536

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.498

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.527

Gnomad4 OTH AF: 0.435

Alfa AF: 0.510 Hom.: 40182

Bravo AF: 0.394

Asia WGS AF: 0.422 AC: 1471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.5
DANN	Benign	0.82

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: rs853308; hg19: chr8-133929917;