Variant 14-81108343-TTCTC-TTCTCTCTC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The ENST00000298171.7(TSHR):c.615-22_615-19dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 1,408,358 control chromosomes in the GnomAD database, including 184,930 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.63 ( 29959 hom., cov: 0)

Exomes 𝑓: 0.55 ( 154971 hom. )

Consequence

TSHR
ENST00000298171.7 intron

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.247

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 14-81108343-T-TTCTC is Benign according to our data. Variant chr14-81108343-T-TTCTC is described in ClinVar as [Likely_benign]. Clinvar id is 255954.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.702 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.615-22_615-19dup		intron_variant		ENST00000298171.7	NP_000360.2
LOC101928462	XR_001751022.2 linkuse as main transcript	n.488-8818_488-8817insGAGA		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSHR	ENST00000298171.7 linkuse as main transcript	c.615-22_615-19dup		intron_variant		1	NM_000369.5	ENSP00000298171	P1
	ENST00000646052.2 linkuse as main transcript	n.511-8818_511-8817insGAGA		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.627

AC:

94591

AN:

150778

Hom.:

29950

Cov.:

show subpopulations

Gnomad AFR

AF:

0.620

Gnomad AMI

AF:

0.430

Gnomad AMR

AF:

0.620

Gnomad ASJ

AF:

0.745

Gnomad EAS

AF:

0.350

Gnomad SAS

AF:

0.722

Gnomad FIN

AF:

0.646

Gnomad MID

AF:

0.719

Gnomad NFE

AF:

0.640

Gnomad OTH

AF:

0.652

GnomAD3 exomes

AF:

0.530

AC:

102414

AN:

193136

Hom.:

23026

AF XY:

0.531

AC XY:

54931

AN XY:

103378

show subpopulations

Gnomad AFR exome

AF:

0.536

Gnomad AMR exome

AF:

0.538

Gnomad ASJ exome

AF:

0.599

Gnomad EAS exome

AF:

0.293

Gnomad SAS exome

AF:

0.596

Gnomad FIN exome

AF:

0.570

Gnomad NFE exome

AF:

0.544

Gnomad OTH exome

AF:

0.554

GnomAD4 exome

AF:

0.549

AC:

690441

AN:

1257464

Hom.:

154971

Cov.:

AF XY:

0.550

AC XY:

348348

AN XY:

633040

show subpopulations

Gnomad4 AFR exome

AF:

0.534

Gnomad4 AMR exome

AF:

0.550

Gnomad4 ASJ exome

AF:

0.611

Gnomad4 EAS exome

AF:

0.338

Gnomad4 SAS exome

AF:

0.595

Gnomad4 FIN exome

AF:

0.565

Gnomad4 NFE exome

AF:

0.552

Gnomad4 OTH exome

AF:

0.545

GnomAD4 genome

AF:

0.627

AC:

94647

AN:

150894

Hom.:

29959

Cov.:

AF XY:

0.624

AC XY:

45999

AN XY:

73680

show subpopulations

Gnomad4 AFR

AF:

0.620

Gnomad4 AMR

AF:

0.619

Gnomad4 ASJ

AF:

0.745

Gnomad4 EAS

AF:

0.350

Gnomad4 SAS

AF:

0.723

Gnomad4 FIN

AF:

0.646

Gnomad4 NFE

AF:

0.640

Gnomad4 OTH

AF:

0.650

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TSHR-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 01, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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