2-1404043-C-T

Position:

• chr2-1404043-C-T

Variant summary

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

The ENST00000497517.6(TPO):​n.180+29641C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 152,078 control chromosomes in the GnomAD database, including 11,702 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 0.39 (11702 hom., cov: 33)
• Consequence: TPO ENST00000497517.6 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPO	XM_047445652.1	c.-536C>T		5_prime_UTR_variant	2/19
TPO	XM_047445653.1	c.-536C>T		5_prime_UTR_variant	2/19
TPO	XM_047445654.1	c.-300C>T		5_prime_UTR_variant	2/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPO	ENST00000497517.6	n.180+29641C>T		intron_variant, non_coding_transcript_variant		1
	ENST00000650512.1	n.865+5486G>A		intron_variant, non_coding_transcript_variant
TPO	ENST00000650224.1	n.378C>T		non_coding_transcript_exon_variant	2/4

Frequencies

GnomAD3 genomes AF: 0.388 AC: 59013 AN: 151960 Hom.: 11690 Cov.: 33

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.383

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

GnomAD4 genome AF: 0.388 AC: 59058 AN: 152078 Hom.: 11702 Cov.: 33 AF XY: 0.389 AC XY: 28913 AN XY: 74328

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.472

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.383

Alfa AF: 0.398 Hom.: 11324

Bravo AF: 0.386

Asia WGS AF: 0.409 AC: 1421 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	0.090
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11675434; hg19: chr2-1407815;