8-132966866-A-G

Variant names:

• chr8-132966866-A-G
• rs7829428
• NM_003235.5:c.5686+169A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

TG Gene-Disease associations (from GenCC):

• thyroid dyshormonogenesis 3

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• familial thyroid dyshormonogenesis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• thyroid cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003235.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TG	NM_003235.5	MANE Select	c.5686+169A>G		intron	N/A	NP_003226.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TG	ENST00000220616.9	TSL:1 MANE Select	c.5686+169A>G		intron	N/A	ENSP00000220616.4
	TG	ENST00000518058.1	TSL:1	c.80-928A>G		intron	N/A	ENSP00000429164.1
	TG	ENST00000523756.5	TSL:1	n.*1899+169A>G		intron	N/A	ENSP00000428628.1

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

African (AFR) AF: 0.433 AC: 17973 AN: 41482

American (AMR) AF: 0.244 AC: 3729 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 794 AN: 3470

East Asian (EAS) AF: 0.480 AC: 2483 AN: 5168

South Asian (SAS) AF: 0.310 AC: 1494 AN: 4818

European-Finnish (FIN) AF: 0.136 AC: 1439 AN: 10598

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11636 AN: 67988

Other (OTH) AF: 0.254 AC: 535 AN: 2108

Alfa AF: 0.233 Hom.: 645

Bravo AF: 0.281

Asia WGS AF: 0.351 AC: 1219 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.48
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7829428; hg19: chr8-133979111;