Variant chr8-132868089-T-C 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.68-26T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.992 in 1,610,584 control chromosomes in the GnomAD database, including 791,804 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.99 ( 75347 hom., cov: 31)

Exomes 𝑓: 0.99 ( 716457 hom. )

Consequence

TG
NM_003235.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.169

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 8-132868089-T-C is Benign according to our data. Variant chr8-132868089-T-C is described in ClinVar as [Benign]. Clinvar id is 1271560.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TG	NM_003235.5 linkuse as main transcript	c.68-26T>C		intron_variant		ENST00000220616.9	NP_003226.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TG	ENST00000220616.9 linkuse as main transcript	c.68-26T>C		intron_variant		1	NM_003235.5	ENSP00000220616	P1	P01266-1
TG	ENST00000523901.1 linkuse as main transcript	c.68-26T>C		intron_variant, NMD_transcript_variant		5		ENSP00000427871

Frequencies

GnomAD3 genomes

AF:

0.995

AC:

151371

AN:

152176

Hom.:

75288

Cov.:

show subpopulations

Gnomad AFR

AF:

0.998

Gnomad AMI

AF:

0.992

Gnomad AMR

AF:

0.995

Gnomad ASJ

AF:

0.999

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

0.998

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

0.991

Gnomad OTH

AF:

0.994

GnomAD3 exomes

AF:

0.995

AC:

249825

AN:

251068

Hom.:

124295

AF XY:

0.995

AC XY:

135051

AN XY:

135728

show subpopulations

Gnomad AFR exome

AF:

0.999

Gnomad AMR exome

AF:

0.996

Gnomad ASJ exome

AF:

0.999

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.998

Gnomad NFE exome

AF:

0.991

Gnomad OTH exome

AF:

0.992

GnomAD4 exome

AF:

0.991

AC:

1445524

AN:

1458290

Hom.:

716457

Cov.:

AF XY:

0.992

AC XY:

719696

AN XY:

725728

show subpopulations

Gnomad4 AFR exome

AF:

0.999

Gnomad4 AMR exome

AF:

0.996

Gnomad4 ASJ exome

AF:

0.999

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

0.997

Gnomad4 NFE exome

AF:

0.989

Gnomad4 OTH exome

AF:

0.992

GnomAD4 genome

AF:

0.995

AC:

151489

AN:

152294

Hom.:

75347

Cov.:

AF XY:

0.995

AC XY:

74101

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.998

Gnomad4 AMR

AF:

0.995

Gnomad4 ASJ

AF:

0.999

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

0.998

Gnomad4 NFE

AF:

0.991

Gnomad4 OTH

AF:

0.994

Alfa

AF:

0.994

Hom.:

13386

Bravo

AF:

0.994

Asia WGS

AF:

0.999

AC:

3475

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Iodotyrosyl coupling defect

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

7.2

DANN

Benign

0.58

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