rs2979033

Positions:

• chr8-133110452-A-G
• chr8-133110452-A-T

Variant summary

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

The NM_003235.5(TG):​c.7573-2970A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 152,228 control chromosomes in the GnomAD database, including 44,840 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 0.76 (44840 hom., cov: 33)
• Consequence: TG NM_003235.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TG	NM_003235.5	c.7573-2970A>G		intron_variant		ENST00000220616.9	NP_003226.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TG	ENST00000220616.9	c.7573-2970A>G		intron_variant		1	NM_003235.5	ENSP00000220616	P1

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115309 AN: 152110 Hom.: 44792 Cov.: 33

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.789

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.768

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.752

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

GnomAD4 genome AF: 0.758 AC: 115401 AN: 152228 Hom.: 44840 Cov.: 33 AF XY: 0.750 AC XY: 55799 AN XY: 74410

Gnomad4 AFR AF: 0.908

Gnomad4 AMR AF: 0.648

Gnomad4 ASJ AF: 0.789

Gnomad4 EAS AF: 0.396

Gnomad4 SAS AF: 0.613

Gnomad4 FIN AF: 0.702

Gnomad4 NFE AF: 0.737

Gnomad4 OTH AF: 0.745

Alfa AF: 0.763 Hom.: 6184

Bravo AF: 0.757

Asia WGS AF: 0.493 AC: 1719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.27

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: rs2979033; hg19: chr8-134122696;