Variant chr8-133050021-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003235.5(TG):c.7239+19998A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,396,346 control chromosomes in the GnomAD database, including 27,678 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 0.16 ( 2828 hom., cov: 33)

Exomes 𝑓: 0.17 ( 24850 hom. )

Consequence

TG
NM_003235.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.50

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:

SLA (HGNC:10902): (Src like adaptor) Predicted to enable signaling receptor binding activity. Predicted to be involved in cell differentiation; innate immune response; and transmembrane receptor protein tyrosine kinase signaling pathway. Predicted to be located in cytosol. Predicted to be active in dendritic spine and focal adhesion. Predicted to be extrinsic component of cytoplasmic side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLA links:

SLA (HGNC:):

SLA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 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.7239+19998A>G		intron_variant		ENST00000220616.9	NP_003226.4	P01266-1
SLA	NM_001045556.3 linkuse as main transcript	c.162-33T>C		intron_variant		ENST00000338087.10	NP_001039021.1	Q13239-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TG	ENST00000220616.9 linkuse as main transcript	c.7239+19998A>G		intron_variant		1	NM_003235.5	ENSP00000220616.4		P01266-1
SLA	ENST00000338087.10 linkuse as main transcript	c.162-33T>C		intron_variant		1	NM_001045556.3	ENSP00000337548.5		Q13239-1

Frequencies

GnomAD3 genomes

AF:

0.162

AC:

24684

AN:

152144

Hom.:

2821

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0908

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.297

Gnomad ASJ

AF:

0.166

Gnomad EAS

AF:

0.520

Gnomad SAS

AF:

0.354

Gnomad FIN

AF:

0.188

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.130

Gnomad OTH

AF:

0.176

GnomAD3 exomes

AF:

0.226

AC:

56791

AN:

250892

Hom.:

8859

AF XY:

0.224

AC XY:

30374

AN XY:

135624

show subpopulations

Gnomad AFR exome

AF:

0.0876

Gnomad AMR exome

AF:

0.398

Gnomad ASJ exome

AF:

0.157

Gnomad EAS exome

AF:

0.520

Gnomad SAS exome

AF:

0.342

Gnomad FIN exome

AF:

0.185

Gnomad NFE exome

AF:

0.131

Gnomad OTH exome

AF:

0.198

GnomAD4 exome

AF:

0.172

AC:

214218

AN:

1244084

Hom.:

24850

Cov.:

AF XY:

0.176

AC XY:

111028

AN XY:

630572

show subpopulations

Gnomad4 AFR exome

AF:

0.0901

Gnomad4 AMR exome

AF:

0.380

Gnomad4 ASJ exome

AF:

0.158

Gnomad4 EAS exome

AF:

0.554

Gnomad4 SAS exome

AF:

0.338

Gnomad4 FIN exome

AF:

0.182

Gnomad4 NFE exome

AF:

0.133

Gnomad4 OTH exome

AF:

0.182

GnomAD4 genome

AF:

0.162

AC:

24695

AN:

152262

Hom.:

2828

Cov.:

AF XY:

0.173

AC XY:

12888

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0908

Gnomad4 AMR

AF:

0.297

Gnomad4 ASJ

AF:

0.166

Gnomad4 EAS

AF:

0.521

Gnomad4 SAS

AF:

0.351

Gnomad4 FIN

AF:

0.188

Gnomad4 NFE

AF:

0.130

Gnomad4 OTH

AF:

0.180

Alfa

AF:

0.159

Hom.:

633

Bravo

AF:

0.167

Asia WGS

AF:

0.431

AC:

1496

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.0040

DANN

Benign

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over