8-132969260-C-T

Position:

• chr8-132969260-C-T

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.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

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=-0.88).
• BP6: Variant 8-132969260-C-T is Benign according to our data. Variant chr8-132969260-C-T is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TG	NM_003235.5	c.5864-198C>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.5864-198C>T		intron_variant		1	NM_003235.5	ENSP00000220616.4
TG	ENST00000523756.5	n.*2077-198C>T		intron_variant		1		ENSP00000428628.1
TG	ENST00000519178.5	c.1229-198C>T		intron_variant		2		ENSP00000430523.1
TG	ENST00000519543.5	c.326-198C>T		intron_variant		2		ENSP00000430430.1

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

Gnomad4 AFR AF: 0.614

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.409

Alfa AF: 0.339 Hom.: 6181

Bravo AF: 0.440

Asia WGS AF: 0.308 AC: 1070 AN: 3478

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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.35

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: rs2687809; hg19: chr8-133981505; COSMIC: COSV55082791; COSMIC: COSV55082791;