Variant 14-81108501-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000298171.7(TSHR):c.692+49T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.02 in 1,505,526 control chromosomes in the GnomAD database, including 521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 26 hom., cov: 25)

Exomes 𝑓: 0.021 ( 495 hom. )

Consequence

TSHR
ENST00000298171.7 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0880

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:

TSHR (HGNC:):

TSHR 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=-0.86).

BP6

Variant 14-81108501-T-C is Benign according to our data. Variant chr14-81108501-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 403571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0143 (2088/146066) while in subpopulation NFE AF= 0.0214 (1427/66558). AF 95% confidence interval is 0.0205. There are 26 homozygotes in gnomad4. There are 966 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 26 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSHR	NM_000369.5 linkuse as main transcript	c.692+49T>C		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.692+49T>C		intron_variant		1	NM_000369.5	ENSP00000298171.2		A0A0A0MTJ0

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

2088

AN:

146018

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00446

Gnomad AMI

AF:

0.00111

Gnomad AMR

AF:

0.0162

Gnomad ASJ

AF:

0.0185

Gnomad EAS

AF:

0.000394

Gnomad SAS

AF:

0.0100

Gnomad FIN

AF:

0.0107

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0214

Gnomad OTH

AF:

0.0204

GnomAD4 exome

AF:

0.0206

AC:

28014

AN:

1359460

Hom.:

495

Cov.:

AF XY:

0.0202

AC XY:

13676

AN XY:

676716

show subpopulations

Gnomad4 AFR exome

AF:

0.00342

Gnomad4 AMR exome

AF:

0.0109

Gnomad4 ASJ exome

AF:

0.0239

Gnomad4 EAS exome

AF:

0.000155

Gnomad4 SAS exome

AF:

0.0126

Gnomad4 FIN exome

AF:

0.00856

Gnomad4 NFE exome

AF:

0.0234

Gnomad4 OTH exome

AF:

0.0200

GnomAD4 genome

AF:

0.0143

AC:

2088

AN:

146066

Hom.:

Cov.:

AF XY:

0.0136

AC XY:

966

AN XY:

70800

show subpopulations

Gnomad4 AFR

AF:

0.00445

Gnomad4 AMR

AF:

0.0162

Gnomad4 ASJ

AF:

0.0185

Gnomad4 EAS

AF:

0.000395

Gnomad4 SAS

AF:

0.0101

Gnomad4 FIN

AF:

0.0107

Gnomad4 NFE

AF:

0.0214

Gnomad4 OTH

AF:

0.0202

Alfa

AF:

0.341

Hom.:

2601

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: classification based on high MAF (>1% in 1000Genomes), outside of splice consensus sequence and lack of conservation -

Familial gestational hyperthyroidism

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Hypothyroidism due to TSH receptor mutations

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Familial hyperthyroidism due to mutations in TSH receptor

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.2

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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