rs8017455

Positions:

• chr14-81109110-T-C

Variant summary

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

The NM_000369.5(TSHR):​c.692+658T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,080 control chromosomes in the GnomAD database, including 3,585 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 0.21 (3585 hom., cov: 31)
• Consequence: TSHR NM_000369.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339

Genes affected

TSHR (HGNC:12373): (thyroid stimulating hormone receptor) The protein encoded by this gene is a membrane protein and a major controller of thyroid cell metabolism. The encoded protein is a receptor for thyrothropin and thyrostimulin, and its activity is mediated by adenylate cyclase. Defects in this gene are a cause of several types of hyperthyroidism. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSHR	NM_000369.5	c.692+658T>C		intron_variant		ENST00000298171.7	NP_000360.2
LOC101928462	XR_001751022.2	n.488-9584A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSHR	ENST00000298171.7	c.692+658T>C		intron_variant		1	NM_000369.5	ENSP00000298171	P1
	ENST00000646052.2	n.511-9584A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31406 AN: 151962 Hom.: 3584 Cov.: 31

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.207 AC: 31435 AN: 152080 Hom.: 3585 Cov.: 31 AF XY: 0.207 AC XY: 15368 AN XY: 74328

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.164

Alfa AF: 0.171 Hom.: 5242

Bravo AF: 0.208

Asia WGS AF: 0.173 AC: 600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.3
DANN	Benign	0.41

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: rs8017455; hg19: chr14-81575454;