Variant 8-132948746-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003235.5(TG):c.5234-30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 1,611,312 control chromosomes in the GnomAD database, including 503,523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 48190 hom., cov: 31)

Exomes 𝑓: 0.79 ( 455333 hom. )

Consequence

TG
NM_003235.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.60

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 8-132948746-C-T is Benign according to our data. Variant chr8-132948746-C-T is described in ClinVar as [Benign]. Clinvar id is 1246261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TG	NM_003235.5 linkuse as main transcript	c.5234-30C>T		intron_variant		ENST00000220616.9

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
TG	ENST00000220616.9 linkuse as main transcript	c.5234-30C>T	intron_variant	1	NM_003235.5	P1	P01266-1
TG	ENST00000523756.5 linkuse as main transcript	c.*1447-30C>T	intron_variant, NMD_transcript_variant	1
TG	ENST00000519178.5 linkuse as main transcript	c.600-30C>T	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.796

AC:

120903

AN:

151968

Hom.:

48152

Cov.:

show subpopulations

Gnomad AFR

AF:

0.798

Gnomad AMI

AF:

0.792

Gnomad AMR

AF:

0.850

Gnomad ASJ

AF:

0.742

Gnomad EAS

AF:

0.801

Gnomad SAS

AF:

0.831

Gnomad FIN

AF:

0.797

Gnomad MID

AF:

0.835

Gnomad NFE

AF:

0.781

Gnomad OTH

AF:

0.794

GnomAD3 exomes

AF:

0.808

AC:

203189

AN:

251320

Hom.:

82372

AF XY:

0.807

AC XY:

109660

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.798

Gnomad AMR exome

AF:

0.894

Gnomad ASJ exome

AF:

0.747

Gnomad EAS exome

AF:

0.804

Gnomad SAS exome

AF:

0.837

Gnomad FIN exome

AF:

0.797

Gnomad NFE exome

AF:

0.785

Gnomad OTH exome

AF:

0.796

GnomAD4 exome

AF:

0.789

AC:

1151730

AN:

1459226

Hom.:

455333

Cov.:

AF XY:

0.790

AC XY:

573633

AN XY:

726010

show subpopulations

Gnomad4 AFR exome

AF:

0.797

Gnomad4 AMR exome

AF:

0.886

Gnomad4 ASJ exome

AF:

0.747

Gnomad4 EAS exome

AF:

0.805

Gnomad4 SAS exome

AF:

0.841

Gnomad4 FIN exome

AF:

0.797

Gnomad4 NFE exome

AF:

0.781

Gnomad4 OTH exome

AF:

0.785

GnomAD4 genome

AF:

0.796

AC:

120988

AN:

152086

Hom.:

48190

Cov.:

AF XY:

0.797

AC XY:

59228

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.798

Gnomad4 AMR

AF:

0.850

Gnomad4 ASJ

AF:

0.742

Gnomad4 EAS

AF:

0.801

Gnomad4 SAS

AF:

0.831

Gnomad4 FIN

AF:

0.797

Gnomad4 NFE

AF:

0.781

Gnomad4 OTH

AF:

0.784

Alfa

AF:

0.767

Hom.:

8889

Bravo

AF:

0.800

Asia WGS

AF:

0.780

AC:

2715

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Iodotyrosyl coupling defect

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

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

-0.97

CADD

Benign

0.0080

DANN

Benign

0.43

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over