rs1514685

Positions:

• chr2-1435493-T-G

Variant summary

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

The NM_001206744.2(TPO):​c.350-759T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,052 control chromosomes in the GnomAD database, including 8,277 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 0.32 (8277 hom., cov: 33)
• Consequence: TPO NM_001206744.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPO	NM_001206744.2	c.350-759T>G		intron_variant		ENST00000329066.9	NP_001193673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPO	ENST00000329066.9	c.350-759T>G		intron_variant		1	NM_001206744.2	ENSP00000329869.4

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47810 AN: 151934 Hom.: 8239 Cov.: 33

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.315 AC: 47907 AN: 152052 Hom.: 8277 Cov.: 33 AF XY: 0.321 AC XY: 23878 AN XY: 74328

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.484

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.329

Alfa AF: 0.281 Hom.: 1013

Bravo AF: 0.323

Asia WGS AF: 0.416 AC: 1445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0020
DANN	Benign	0.48

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

Other links and lift over

dbSNP: rs1514685; hg19: chr2-1439265;