rs2687809

Variant names:

• chr8-132969260-C-T
• rs2687809
• NM_003235.5:c.5864-198C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-132969260-C-T
• chr8-132969260-C-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003235.5(TG):​c.5864-198C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 151,778 control chromosomes in the GnomAD database, including 15,551 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.44 (15551 hom., cov: 31)
• Consequence: TG NM_003235.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.455
• Publications: 3 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: PanelApp Australia, 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 8-132969260-C-T is Benign according to our data. Variant chr8-132969260-C-T is described in ClinVar as Benign. ClinVar VariationId is 1259745.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TG	NM_003235.5	MANE Select	c.5864-198C>T		intron	N/A	NP_003226.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TG	ENST00000220616.9	TSL:1 MANE Select	c.5864-198C>T		intron	N/A	ENSP00000220616.4	P01266-1
	TG	ENST00000523756.5	TSL:1	n.*2077-198C>T		intron	N/A	ENSP00000428628.1	H0YB42
	TG	ENST00000519178.5	TSL:2	c.1229-198C>T		intron	N/A	ENSP00000430523.1	H0YBY1

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66051 AN: 151660 Hom.: 15519 Cov.: 31

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.436 AC: 66133 AN: 151778 Hom.: 15551 Cov.: 31 AF XY: 0.436 AC XY: 32346 AN XY: 74198

African (AFR) AF: 0.614 AC: 25383 AN: 41326

American (AMR) AF: 0.420 AC: 6403 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 929 AN: 3470

East Asian (EAS) AF: 0.260 AC: 1342 AN: 5158

South Asian (SAS) AF: 0.296 AC: 1422 AN: 4810

European-Finnish (FIN) AF: 0.433 AC: 4555 AN: 10522

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24855 AN: 67926

Other (OTH) AF: 0.409 AC: 860 AN: 2102

Alfa AF: 0.368 Hom.: 21257

Bravo AF: 0.440

Asia WGS AF: 0.308 AC: 1070 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.35
PhyloP100		-0.46
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: rs2687809; hg19: chr8-133981505; COSMIC: COSV55082791; COSMIC: COSV55082791;