rs7527713

Positions:

• chr1-53900806-G-A
• chr1-53900806-G-C

Variant summary

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

The NM_000792.7(DIO1):​c.338-3860G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 151,398 control chromosomes in the GnomAD database, including 4,160 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 0.23 (4160 hom., cov: 31)
• Consequence: DIO1 NM_000792.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

Genes affected

DIO1 (HGNC:2883): (iodothyronine deiodinase 1) The protein encoded by this gene belongs to the iodothyronine deiodinase family. It catalyzes the activation, as well as the inactivation of thyroid hormone by outer and inner ring deiodination, respectively. The activation reaction involves the conversion of the prohormone thyroxine (3,5,3',5'-tetraiodothyronine, T4), secreted by the thyroid gland, to the bioactive thyroid hormone (3,5,3'-triiodothyronine, T3) by 5'-deiodination. This protein provides most of the circulating T3, which is essential for growth, differentiation and basal metabolism in vertebrates. This protein is a selenoprotein, containing the rare amino acid selenocysteine (Sec) at its active site. Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2018]

LOC124904180 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIO1	NM_000792.7	c.338-3860G>A		intron_variant		ENST00000361921.8	NP_000783.2
LOC124904180	XR_007066095.1	n.289-3956C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIO1	ENST00000361921.8	c.338-3860G>A		intron_variant		1	NM_000792.7	ENSP00000354643	P1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34444 AN: 151278 Hom.: 4156 Cov.: 31

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.0773

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.228 AC: 34460 AN: 151398 Hom.: 4160 Cov.: 31 AF XY: 0.227 AC XY: 16825 AN XY: 73990

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.219

Alfa AF: 0.203 Hom.: 645

Bravo AF: 0.240

Asia WGS AF: 0.282 AC: 982 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.34

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: rs7527713; hg19: chr1-54366479;