8-132966866-A-G

Variant summary

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

The NM_003235.5(TG):c.5686+169A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,118 control chromosomes in the GnomAD database, including 6,436 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 0.27 (6436 hom., cov: 32)
• Consequence: TG NM_003235.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TG	NM_003235.5	c.5686+169A>G		intron_variant		ENST00000220616.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TG	ENST00000220616.9	c.5686+169A>G		intron_variant		1	NM_003235.5	P1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40329 AN: 152000 Hom.: 6404 Cov.: 32

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.266 AC: 40397 AN: 152118 Hom.: 6436 Cov.: 32 AF XY: 0.265 AC XY: 19692 AN XY: 74362

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.254

Alfa AF: 0.224 Hom.: 558

Bravo AF: 0.281

Asia WGS AF: 0.351 AC: 1219 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.2
Dann	Benign	0.48

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: rs7829428; hg19: chr8-133979111;