8-133128302-C-T

Position:

• chr8-133128302-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.7863-3510C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 146,258 control chromosomes in the GnomAD database, including 3,858 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 0.21 (3858 hom., cov: 28)
• Consequence: TG NM_003235.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TG	NM_003235.5	c.7863-3510C>T		intron_variant		ENST00000220616.9	NP_003226.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TG	ENST00000220616.9	c.7863-3510C>T		intron_variant		1	NM_003235.5	ENSP00000220616.4

Frequencies

GnomAD3 genomes AF: 0.215 AC: 31422 AN: 146148 Hom.: 3859 Cov.: 28

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.00316

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.215 AC: 31427 AN: 146258 Hom.: 3858 Cov.: 28 AF XY: 0.209 AC XY: 14780 AN XY: 70850

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.00317

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.236

Alfa AF: 0.246 Hom.: 6103

Bravo AF: 0.218

Asia WGS AF: 0.0690 AC: 237 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.19
DANN	Benign	0.76

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: rs17705719; hg19: chr8-134140546;