Variant rs2241119 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000369.5(TSHR):c.545+13A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,610,764 control chromosomes in the GnomAD database, including 28,193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 7444 hom., cov: 32)

Exomes 𝑓: 0.15 ( 20749 hom. )

Consequence

TSHR
NM_000369.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.113

Variant links:

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]

TSHR links:

LOC101928462 (HGNC:):

LOC101928462 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 14-81092621-A-G is Benign according to our data. Variant chr14-81092621-A-G is described in ClinVar as [Benign]. Clinvar id is 255952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-81092621-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSHR	NM_000369.5 linkuse as main transcript	c.545+13A>G		intron_variant		ENST00000298171.7	NP_000360.2	P16473A0A0A0MTJ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSHR	ENST00000298171.7 linkuse as main transcript	c.545+13A>G		intron_variant		1	NM_000369.5	ENSP00000298171.2		A0A0A0MTJ0

Frequencies

GnomAD3 genomes

AF:

0.256

AC:

38857

AN:

151896

Hom.:

7414

Cov.:

show subpopulations

Gnomad AFR

AF:

0.537

Gnomad AMI

AF:

0.231

Gnomad AMR

AF:

0.150

Gnomad ASJ

AF:

0.152

Gnomad EAS

AF:

0.328

Gnomad SAS

AF:

0.170

Gnomad FIN

AF:

0.157

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.133

Gnomad OTH

AF:

0.195

GnomAD3 exomes

AF:

0.180

AC:

45239

AN:

251226

Hom.:

5638

AF XY:

0.173

AC XY:

23445

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.548

Gnomad AMR exome

AF:

0.123

Gnomad ASJ exome

AF:

0.145

Gnomad EAS exome

AF:

0.337

Gnomad SAS exome

AF:

0.162

Gnomad FIN exome

AF:

0.151

Gnomad NFE exome

AF:

0.135

Gnomad OTH exome

AF:

0.151

GnomAD4 exome

AF:

0.150

AC:

218875

AN:

1458752

Hom.:

20749

Cov.:

AF XY:

0.149

AC XY:

108322

AN XY:

725930

show subpopulations

Gnomad4 AFR exome

AF:

0.558

Gnomad4 AMR exome

AF:

0.127

Gnomad4 ASJ exome

AF:

0.144

Gnomad4 EAS exome

AF:

0.324

Gnomad4 SAS exome

AF:

0.162

Gnomad4 FIN exome

AF:

0.149

Gnomad4 NFE exome

AF:

0.131

Gnomad4 OTH exome

AF:

0.167

GnomAD4 genome

AF:

0.256

AC:

38940

AN:

152012

Hom.:

7444

Cov.:

AF XY:

0.254

AC XY:

18903

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.538

Gnomad4 AMR

AF:

0.150

Gnomad4 ASJ

AF:

0.152

Gnomad4 EAS

AF:

0.328

Gnomad4 SAS

AF:

0.169

Gnomad4 FIN

AF:

0.157

Gnomad4 NFE

AF:

0.133

Gnomad4 OTH

AF:

0.195

Alfa

AF:

0.151

Hom.:

3891

Bravo

AF:

0.271

Asia WGS

AF:

0.254

AC:

884

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Hypothyroidism due to TSH receptor mutations

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Familial hyperthyroidism due to mutations in TSH receptor

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over