17-40062520-G-C

Variant names:

• chr17-40062520-G-C
• rs62065216
• ENST00000578218:c.-326G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001190919.2(THRA):​c.-298+69G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
• Consequence: THRA NM_001190919.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.81

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THRA	NM_001190919.2	c.-298+69G>C		intron_variant	Intron 1 of 9		NP_001177848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THRA	ENST00000578218	c.-326G>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 5	4		ENSP00000464123.1
THRA	ENST00000578218	c.-326G>C		5_prime_UTR_variant	Exon 1 of 5	4		ENSP00000464123.1
THRA	ENST00000394121.8	c.-298+69G>C		intron_variant	Intron 1 of 9	2		ENSP00000377679.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	15
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs62065216; hg19: chr17-38218773;