rs2268474

chr14-81058063-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.171-4085T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,174 control chromosomes in the GnomAD database, including 4,940 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 0.25 (4940 hom., cov: 33)
• Consequence: TSHR NM_000369.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116

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 (SAS) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSHR	NM_000369.5	c.171-4085T>C		intron_variant		ENST00000298171.7
LOC101928462	XR_001751022.2	n.1068-4247A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSHR	ENST00000298171.7	c.171-4085T>C		intron_variant		1	NM_000369.5	P1
	ENST00000646052.2	n.1091-4247A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38345 AN: 152056 Hom.: 4943 Cov.: 33

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.252 AC: 38365 AN: 152174 Hom.: 4940 Cov.: 33 AF XY: 0.250 AC XY: 18631 AN XY: 74404

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.260

Alfa AF: 0.252 Hom.: 2967

Bravo AF: 0.250

Asia WGS AF: 0.278 AC: 970 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	4.1
Dann	Benign	0.79

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: rs2268474; hg19: chr14-81524407;