rs11694732

Positions:

• chr2-1404578-G-C
• chr2-1404578-G-T

Variant summary

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

The ENST00000497517.6(TPO):​n.180+30176G>C 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 0.39 in 152,006 control chromosomes in the GnomAD database, including 11,761 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 (11761 hom., cov: 32)
• Consequence: TPO ENST00000497517.6 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.760

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPO	XM_024453089.2	c.-480-2415G>C		intron_variant			XP_024308857.1
TPO	XM_047445652.1	c.-481+480G>C		intron_variant			XP_047301608.1
TPO	XM_047445653.1	c.-481+480G>C		intron_variant			XP_047301609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPO	ENST00000497517.6	n.180+30176G>C		intron_variant, non_coding_transcript_variant		1
	ENST00000650512.1	n.865+4951C>G		intron_variant, non_coding_transcript_variant
TPO	ENST00000650224.1	n.433+480G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59209 AN: 151888 Hom.: 11749 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.390 AC: 59255 AN: 152006 Hom.: 11761 Cov.: 32 AF XY: 0.390 AC XY: 28997 AN XY: 74288

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.386

Alfa AF: 0.288 Hom.: 762

Bravo AF: 0.388

Asia WGS AF: 0.411 AC: 1425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.3
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11694732; hg19: chr2-1408350;