rs2294025

Positions:

• chr8-133133268-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003235.5(TG):​c.7998-202G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 646,410 control chromosomes in the GnomAD database, including 68,190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.48 (18012 hom., cov: 32)
  • Exomes 𝑓: 0.44 (50178 hom.)
• Consequence: TG NM_003235.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.33

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 8-133133268-G-A is Benign according to our data. Variant chr8-133133268-G-A is described in ClinVar as [Benign]. Clinvar id is 1279842.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TG	NM_003235.5	c.7998-202G>A		intron_variant		ENST00000220616.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TG	ENST00000220616.9	c.7998-202G>A		intron_variant		1	NM_003235.5	P1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72661 AN: 151834 Hom.: 18003 Cov.: 32

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.501

GnomAD4 exome AF: 0.438 AC: 216331 AN: 494458 Hom.: 50178 AF XY: 0.432 AC XY: 113906 AN XY: 263466

Gnomad4 AFR exome AF: 0.549

Gnomad4 AMR exome AF: 0.406

Gnomad4 ASJ exome AF: 0.556

Gnomad4 EAS exome AF: 0.122

Gnomad4 SAS exome AF: 0.322

Gnomad4 FIN exome AF: 0.399

Gnomad4 NFE exome AF: 0.484

Gnomad4 OTH exome AF: 0.468

GnomAD4 genome AF: 0.478 AC: 72697 AN: 151952 Hom.: 18012 Cov.: 32 AF XY: 0.467 AC XY: 34701 AN XY: 74286

Gnomad4 AFR AF: 0.554

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.566

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.496

Alfa AF: 0.475 Hom.: 8891

Bravo AF: 0.488

Asia WGS AF: 0.234 AC: 815 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.5
DANN	Benign	0.72

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: rs2294025; hg19: chr8-134145512;