Variant 8-109087635-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_003301.7(TRHR):c.123A>G(p.Val41=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00352 in 1,614,168 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 9 hom. )

Consequence

TRHR
NM_003301.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.459

Variant links:

Genes affected

TRHR (HGNC:12299): (thyrotropin releasing hormone receptor) This gene encodes a G protein-coupled receptor for thyrotropin-releasing hormone (TRH). Upon binding to TRH, this receptor activates the inositol phospholipid-calcium-protein kinase C transduction pathway. Mutations in this gene have been associated with generalized thyrotropin-releasing hormone resistance. [provided by RefSeq, Sep 2011]

TRHR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 8-109087635-A-G is Benign according to our data. Variant chr8-109087635-A-G is described in ClinVar as [Benign]. Clinvar id is 715012.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-109087635-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.459 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRHR	NM_003301.7 linkuse as main transcript	c.123A>G	p.Val41=	synonymous_variant	2/3	ENST00000518632.2	NP_003292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRHR	ENST00000518632.2 linkuse as main transcript	c.123A>G	p.Val41=	synonymous_variant	2/3	5	NM_003301.7	ENSP00000430711	P1
TRHR	ENST00000311762.2 linkuse as main transcript	c.123A>G	p.Val41=	synonymous_variant	1/2	1		ENSP00000309818	P1

Frequencies

GnomAD3 genomes

AF:

0.00217

AC:

330

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00424

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00378

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00209

AC:

526

AN:

251386

Hom.:

AF XY:

0.00216

AC XY:

294

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.00319

Gnomad NFE exome

AF:

0.00357

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00366

AC:

5352

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00352

AC XY:

2562

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000661

Gnomad4 FIN exome

AF:

0.00324

Gnomad4 NFE exome

AF:

0.00447

Gnomad4 OTH exome

AF:

0.00205

GnomAD4 genome

AF:

0.00217

AC:

330

AN:

152282

Hom.:

Cov.:

AF XY:

0.00212

AC XY:

158

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00424

Gnomad4 NFE

AF:

0.00378

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00286

Hom.:

Bravo

AF:

0.00177

EpiCase

AF:

0.00316

EpiControl

AF:

0.00302

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

TRHR-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 22, 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

BayesDel_noAF

Benign

-0.56

CADD

Benign

7.2

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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