rs2284735

Positions:

• chr14-81087442-A-G
• chr14-81087442-A-T

Variant summary

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

The NM_000369.5(TSHR):​c.318-512A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 180,886 control chromosomes in the GnomAD database, including 24,523 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 0.46 (19585 hom., cov: 32)
  • Exomes 𝑓: 0.57 (4938 hom.)
• Consequence: TSHR NM_000369.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119

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=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSHR	NM_000369.5	c.318-512A>G		intron_variant		ENST00000298171.7
LOC101928462	XR_001751022.2	n.1067+25T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSHR	ENST00000298171.7	c.318-512A>G		intron_variant		1	NM_000369.5	P1
	ENST00000646052.2	n.1090+25T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69619 AN: 151858 Hom.: 19589 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.500

GnomAD4 exome AF: 0.568 AC: 16412 AN: 28910 Hom.: 4938 Cov.: 0 AF XY: 0.553 AC XY: 8312 AN XY: 15022

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.593

Gnomad4 ASJ exome AF: 0.527

Gnomad4 EAS exome AF: 0.405

Gnomad4 SAS exome AF: 0.442

Gnomad4 FIN exome AF: 0.661

Gnomad4 NFE exome AF: 0.609

Gnomad4 OTH exome AF: 0.568

GnomAD4 genome AF: 0.458 AC: 69625 AN: 151976 Hom.: 19585 Cov.: 32 AF XY: 0.456 AC XY: 33863 AN XY: 74262

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.524

Gnomad4 ASJ AF: 0.586

Gnomad4 EAS AF: 0.423

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.642

Gnomad4 NFE AF: 0.617

Gnomad4 OTH AF: 0.500

Alfa AF: 0.591 Hom.: 44209

Bravo AF: 0.437

Asia WGS AF: 0.403 AC: 1399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	2.4
DANN	Benign	0.61

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: rs2284735; hg19: chr14-81553786;