rs938326

Variant names:

• chr2-1398009-C-T
• rs938326
• ENST00000497517.6:n.180+23607C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000898235.1(TPO):​c.-576-5994C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 152,052 control chromosomes in the GnomAD database, including 24,066 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 0.56 (24066 hom., cov: 33)
• Consequence: TPO ENST00000898235.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• thyroid dyshormonogenesis 2A

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• familial thyroid dyshormonogenesis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000231482 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000898235.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPO	ENST00000497517.6	TSL:1	n.180+23607C>T		intron	N/A
	TPO	ENST00000898235.1		c.-576-5994C>T		intron	N/A	ENSP00000568294.1
	TPO	ENST00000898236.1		c.-180-15255C>T		intron	N/A	ENSP00000568295.1

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85008 AN: 151934 Hom.: 24042 Cov.: 33

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.541

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.560 AC: 85084 AN: 152052 Hom.: 24066 Cov.: 33 AF XY: 0.561 AC XY: 41710 AN XY: 74298

African (AFR) AF: 0.624 AC: 25886 AN: 41474

American (AMR) AF: 0.631 AC: 9643 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1824 AN: 3470

East Asian (EAS) AF: 0.604 AC: 3115 AN: 5158

South Asian (SAS) AF: 0.638 AC: 3077 AN: 4826

European-Finnish (FIN) AF: 0.533 AC: 5623 AN: 10556

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34294 AN: 67974

Other (OTH) AF: 0.541 AC: 1143 AN: 2112

Alfa AF: 0.528 Hom.: 71145

Bravo AF: 0.568

Asia WGS AF: 0.618 AC: 2148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.29
DANN	Benign	0.53
PhyloP100		-1.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs938326; hg19: chr2-1401781;