dbSNP rs10189329: TPO:c.2006+20G>A (chr2-1494059-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001206744.2(TPO):c.2006+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0508 in 1,610,738 control chromosomes in the GnomAD database, including 3,486 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.087 ( 982 hom., cov: 33)

Exomes 𝑓: 0.047 ( 2504 hom. )

Consequence

TPO
NM_001206744.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.97

Variant links:

Genes affected

TPO (HGNC:12015): (thyroid peroxidase) This gene encodes a membrane-bound glycoprotein. The encoded protein acts as an enzyme and plays a central role in thyroid gland function. The protein functions in the iodination of tyrosine residues in thyroglobulin and phenoxy-ester formation between pairs of iodinated tyrosines to generate the thyroid hormones, thyroxine and triiodothyronine. Mutations in this gene are associated with several disorders of thyroid hormonogenesis, including congenital hypothyroidism, congenital goiter, and thyroid hormone organification defect IIA. Multiple transcript variants encoding distinct isoforms have been identified for this gene, but the full-length nature of some variants has not been determined. [provided by RefSeq, May 2011]

TPO links:

ENSG00000231482 (HGNC:):

ENSG00000231482 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=-1.06).

BP6

Variant 2-1494059-G-A is Benign according to our data. Variant chr2-1494059-G-A is described in ClinVar as [Benign]. Clinvar id is 256609.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-1494059-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPO	NM_001206744.2 link	c.2006+20G>A		intron_variant	Intron 11 of 16	ENST00000329066.9	NP_001193673.1	P07202-1Q502Y3Q6P534

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPO	ENST00000329066.9 link	c.2006+20G>A		intron_variant	Intron 11 of 16	1	NM_001206744.2	ENSP00000329869.4		P07202-1

Frequencies

GnomAD3 genomes

AF:

0.0871

AC:

13250

AN:

152082

Hom.:

975

Cov.:

show subpopulations

Gnomad AFR

AF:

0.195

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0435

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.104

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.0294

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.0374

Gnomad OTH

AF:

0.0908

GnomAD3 exomes

AF:

0.0604

AC:

15064

AN:

249490

Hom.:

760

AF XY:

0.0596

AC XY:

8048

AN XY:

135092

show subpopulations

Gnomad AFR exome

AF:

0.203

Gnomad AMR exome

AF:

0.0268

Gnomad ASJ exome

AF:

0.0916

Gnomad EAS exome

AF:

0.103

Gnomad SAS exome

AF:

0.0912

Gnomad FIN exome

AF:

0.0299

Gnomad NFE exome

AF:

0.0382

Gnomad OTH exome

AF:

0.0529

GnomAD4 exome

AF:

0.0470

AC:

68609

AN:

1458538

Hom.:

2504

Cov.:

AF XY:

0.0480

AC XY:

34827

AN XY:

725780

show subpopulations

Gnomad4 AFR exome

AF:

0.209

Gnomad4 AMR exome

AF:

0.0299

Gnomad4 ASJ exome

AF:

0.0910

Gnomad4 EAS exome

AF:

0.106

Gnomad4 SAS exome

AF:

0.0881

Gnomad4 FIN exome

AF:

0.0301

Gnomad4 NFE exome

AF:

0.0364

Gnomad4 OTH exome

AF:

0.0605

GnomAD4 genome

AF:

0.0872

AC:

13277

AN:

152200

Hom.:

982

Cov.:

AF XY:

0.0857

AC XY:

6376

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.195

Gnomad4 AMR

AF:

0.0433

Gnomad4 ASJ

AF:

0.107

Gnomad4 EAS

AF:

0.104

Gnomad4 SAS

AF:

0.103

Gnomad4 FIN

AF:

0.0294

Gnomad4 NFE

AF:

0.0374

Gnomad4 OTH

AF:

0.0946

Alfa

AF:

0.0508

Hom.:

319

Bravo

AF:

0.0933

Asia WGS

AF:

0.137

AC:

477

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 20, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.010

DANN

Benign

0.38

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