Variant 3-129976871-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_007117.5(TRH):c.384T>C(p.Asp128=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0697 in 1,612,116 control chromosomes in the GnomAD database, including 4,432 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.072 ( 445 hom., cov: 30)

Exomes 𝑓: 0.070 ( 3987 hom. )

Consequence

TRH
NM_007117.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.978

Variant links:

Genes affected

TRH (HGNC:12298): (thyrotropin releasing hormone) This gene encodes a member of the thyrotropin-releasing hormone family. Cleavage of the encoded proprotein releases mature thyrotropin-releasing hormone, which is a tripeptide hypothalamic regulatory hormone. The human proprotein contains six thyrotropin-releasing hormone tripeptides. Thyrotropin-releasing hormone is involved in the regulation and release of thyroid-stimulating hormone, as well as prolactin. Deficiency of this hormone has been associated with hypothalamic hypothyroidism. [provided by RefSeq, May 2013]

TRH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 3-129976871-T-C is Benign according to our data. Variant chr3-129976871-T-C is described in ClinVar as [Benign]. Clinvar id is 260115.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-129976871-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.978 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRH	NM_007117.5 linkuse as main transcript	c.384T>C	p.Asp128=	synonymous_variant	3/3	ENST00000302649.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRH	ENST00000302649.4 linkuse as main transcript	c.384T>C	p.Asp128=	synonymous_variant	3/3	1	NM_007117.5	P2
TRH	ENST00000507066.1 linkuse as main transcript	c.372T>C	p.Asp124=	synonymous_variant	3/3	5		A1

Frequencies

GnomAD3 genomes

AF:

0.0717

AC:

10755

AN:

150098

Hom.:

445

Cov.:

show subpopulations

Gnomad AFR

AF:

0.100

Gnomad AMI

AF:

0.00221

Gnomad AMR

AF:

0.0682

Gnomad ASJ

AF:

0.0573

Gnomad EAS

AF:

0.00240

Gnomad SAS

AF:

0.0174

Gnomad FIN

AF:

0.0432

Gnomad MID

AF:

0.0517

Gnomad NFE

AF:

0.0702

Gnomad OTH

AF:

0.0802

GnomAD3 exomes

AF:

0.0547

AC:

13756

AN:

251414

Hom.:

453

AF XY:

0.0540

AC XY:

7338

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.0473

Gnomad ASJ exome

AF:

0.0583

Gnomad EAS exome

AF:

0.00506

Gnomad SAS exome

AF:

0.0177

Gnomad FIN exome

AF:

0.0406

Gnomad NFE exome

AF:

0.0699

Gnomad OTH exome

AF:

0.0645

GnomAD4 exome

AF:

0.0695

AC:

101641

AN:

1461892

Hom.:

3987

Cov.:

AF XY:

0.0680

AC XY:

49427

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0998

Gnomad4 AMR exome

AF:

0.0506

Gnomad4 ASJ exome

AF:

0.0568

Gnomad4 EAS exome

AF:

0.00174

Gnomad4 SAS exome

AF:

0.0191

Gnomad4 FIN exome

AF:

0.0422

Gnomad4 NFE exome

AF:

0.0775

Gnomad4 OTH exome

AF:

0.0683

GnomAD4 genome

AF:

0.0716

AC:

10762

AN:

150224

Hom.:

445

Cov.:

AF XY:

0.0691

AC XY:

5065

AN XY:

73296

show subpopulations

Gnomad4 AFR

AF:

0.0998

Gnomad4 AMR

AF:

0.0681

Gnomad4 ASJ

AF:

0.0573

Gnomad4 EAS

AF:

0.00261

Gnomad4 SAS

AF:

0.0172

Gnomad4 FIN

AF:

0.0432

Gnomad4 NFE

AF:

0.0702

Gnomad4 OTH

AF:

0.0793

Alfa

AF:

0.0704

Hom.:

306

Bravo

AF:

0.0754

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.0775

EpiControl

AF:

0.0809

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.53

DANN

Benign

0.35

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