rs1568400

Variant names:

• chr17-40064855-T-C
• rs1568400
• NM_199334.5:c.-298+1763T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-40064855-T-C
• chr17-40064855-T-G

Variant summary

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

The NM_199334.5(THRA):​c.-298+1763T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,000 control chromosomes in the GnomAD database, including 13,543 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 0.38 (13543 hom., cov: 31)
• Consequence: THRA NM_199334.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.919
• Publications: 23 publications found

Genes affected

THRA (HGNC:11796): (thyroid hormone receptor alpha) The protein encoded by this gene is a nuclear hormone receptor for triiodothyronine. It is one of the several receptors for thyroid hormone, and has been shown to mediate the biological activities of thyroid hormone. Knockout studies in mice suggest that the different receptors, while having certain extent of redundancy, may mediate different functions of thyroid hormone. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

THRA Gene-Disease associations (from GenCC):

• congenital nongoitrous hypothyroidism 6

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THRA	NM_199334.5	c.-298+1763T>C		intron_variant	Intron 1 of 8	ENST00000450525.7	NP_955366.1
THRA	NM_001190919.2	c.-298+2404T>C		intron_variant	Intron 1 of 9		NP_001177848.1
THRA	NM_003250.6	c.-298+1763T>C		intron_variant	Intron 1 of 9		NP_003241.2
THRA	NM_001190918.2	c.-298+1763T>C		intron_variant	Intron 1 of 9		NP_001177847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THRA	ENST00000450525.7	c.-298+1763T>C		intron_variant	Intron 1 of 8	1	NM_199334.5	ENSP00000395641.3

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57341 AN: 151882 Hom.: 13521 Cov.: 31

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.378 AC: 57412 AN: 152000 Hom.: 13543 Cov.: 31 AF XY: 0.379 AC XY: 28118 AN XY: 74274

African (AFR) AF: 0.668 AC: 27676 AN: 41428

American (AMR) AF: 0.426 AC: 6502 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 868 AN: 3466

East Asian (EAS) AF: 0.233 AC: 1203 AN: 5170

South Asian (SAS) AF: 0.299 AC: 1437 AN: 4812

European-Finnish (FIN) AF: 0.223 AC: 2353 AN: 10572

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16279 AN: 67966

Other (OTH) AF: 0.344 AC: 726 AN: 2110

Alfa AF: 0.274 Hom.: 11054

Bravo AF: 0.409

Asia WGS AF: 0.271 AC: 945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.42
PhyloP100		-0.92
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: rs1568400; hg19: chr17-38221108;