Variant chr2-1413472-A-G 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_001206744.2(TPO):c.-75A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 162,578 control chromosomes in the GnomAD database, including 26,357 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 24986 hom., cov: 33)

Exomes 𝑓: 0.51 ( 1371 hom. )

Consequence

TPO
NM_001206744.2 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.810

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:

(HGNC:):

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=-0.95).

BP6

Variant 2-1413472-A-G is Benign according to our data. Variant chr2-1413472-A-G is described in ClinVar as [Benign]. Clinvar id is 331215.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPO	NM_001206744.2 linkuse as main transcript	c.-75A>G		5_prime_UTR_variant	1/17	ENST00000329066.9	NP_001193673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPO	ENST00000329066.9 linkuse as main transcript	c.-75A>G		5_prime_UTR_variant	1/17	1	NM_001206744.2	ENSP00000329869	P1	P07202-1
	ENST00000650512.1 linkuse as main transcript	n.647-3725T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.569

AC:

86452

AN:

151944

Hom.:

24955

Cov.:

show subpopulations

Gnomad AFR

AF:

0.636

Gnomad AMI

AF:

0.378

Gnomad AMR

AF:

0.664

Gnomad ASJ

AF:

0.516

Gnomad EAS

AF:

0.653

Gnomad SAS

AF:

0.650

Gnomad FIN

AF:

0.563

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.502

Gnomad OTH

AF:

0.550

GnomAD4 exome

AF:

0.510

AC:

5362

AN:

10516

Hom.:

1371

Cov.:

AF XY:

0.508

AC XY:

2698

AN XY:

5316

show subpopulations

Gnomad4 AFR exome

AF:

0.663

Gnomad4 AMR exome

AF:

0.545

Gnomad4 ASJ exome

AF:

0.589

Gnomad4 EAS exome

AF:

0.600

Gnomad4 SAS exome

AF:

0.700

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.502

Gnomad4 OTH exome

AF:

0.475

GnomAD4 genome

AF:

0.569

AC:

86545

AN:

152062

Hom.:

24986

Cov.:

AF XY:

0.574

AC XY:

42672

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.636

Gnomad4 AMR

AF:

0.665

Gnomad4 ASJ

AF:

0.516

Gnomad4 EAS

AF:

0.653

Gnomad4 SAS

AF:

0.649

Gnomad4 FIN

AF:

0.563

Gnomad4 NFE

AF:

0.502

Gnomad4 OTH

AF:

0.551

Alfa

AF:

0.516

Hom.:

20431

Bravo

AF:

0.577

Asia WGS

AF:

0.649

AC:

2253

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Deficiency of iodide peroxidase

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.8

DANN

Benign

0.64

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