rs670292

Variant names:

• chr6-150381711-C-G
• rs670292
• NM_203395.3:c.179-7641C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_203395.3(IYD):​c.179-7641C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,042 control chromosomes in the GnomAD database, including 13,625 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 0.40 (13625 hom., cov: 32)
• Consequence: IYD NM_203395.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.480
• Publications: 7 publications found

Genes affected

IYD (HGNC:21071): (iodotyrosine deiodinase) This gene encodes an enzyme that catalyzes the oxidative NADPH-dependent deiodination of mono- and diiodotyrosine, which are the halogenated byproducts of thyroid hormone production. The N-terminus of the protein functions as a membrane anchor. Mutations in this gene cause congenital hypothyroidism due to dyshormonogenesis type 4, which is also referred to as deiodinase deficiency, or iodotyrosine dehalogenase deficiency, or thyroid hormonogenesis type 4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

IYD Gene-Disease associations (from GenCC):

• thyroid dyshormonogenesis 4

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• familial thyroid dyshormonogenesis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IYD	NM_203395.3	c.179-7641C>G		intron_variant	Intron 1 of 4	ENST00000344419.8	NP_981932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IYD	ENST00000344419.8	c.179-7641C>G		intron_variant	Intron 1 of 4	1	NM_203395.3	ENSP00000343763.4

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60736 AN: 151924 Hom.: 13634 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.399 AC: 60728 AN: 152042 Hom.: 13625 Cov.: 32 AF XY: 0.391 AC XY: 29044 AN XY: 74308

African (AFR) AF: 0.215 AC: 8902 AN: 41490

American (AMR) AF: 0.403 AC: 6148 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1817 AN: 3472

East Asian (EAS) AF: 0.215 AC: 1114 AN: 5176

South Asian (SAS) AF: 0.276 AC: 1327 AN: 4814

European-Finnish (FIN) AF: 0.420 AC: 4430 AN: 10542

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35532 AN: 67960

Other (OTH) AF: 0.420 AC: 887 AN: 2112

Alfa AF: 0.461 Hom.: 2135

Bravo AF: 0.394

Asia WGS AF: 0.230 AC: 800 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.6
DANN	Benign	0.54
PhyloP100		0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs670292; hg19: chr6-150702847;