rs938326

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_024453089.2(TPO):​c.-480-8984C>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 XM_024453089.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

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]

ENSG00000231482 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPO	XM_024453089.2	c.-480-8984C>T		intron_variant	Intron 1 of 17		XP_024308857.1
TPO	XM_047445652.1	c.-1391-5179C>T		intron_variant	Intron 1 of 18		XP_047301608.1
TPO	XM_047445653.1	c.-576-5994C>T		intron_variant	Intron 1 of 18		XP_047301609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPO	ENST00000497517.6	n.180+23607C>T		intron_variant	Intron 1 of 5	1
TPO	ENST00000650224.1	n.338-5994C>T		intron_variant	Intron 1 of 3
ENSG00000231482	ENST00000650512.1	n.865+11520G>A		intron_variant	Intron 3 of 3

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

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.631

Gnomad4 ASJ AF: 0.526

Gnomad4 EAS AF: 0.604

Gnomad4 SAS AF: 0.638

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.541

Alfa AF: 0.520 Hom.: 21270

Bravo AF: 0.568

Asia WGS AF: 0.618 AC: 2148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs938326; hg19: chr2-1401781;