Variant 3-129977111-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.624T>C(p.Leu208Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.992 in 1,559,382 control chromosomes in the GnomAD database, including 768,447 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.96 ( 70518 hom., cov: 30)

Exomes 𝑓: 1.0 ( 697929 hom. )

Consequence

TRH
NM_007117.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.03

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:

LOC124906284 (HGNC:):

LOC124906284 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=-0.86).

BP6

Variant 3-129977111-T-C is Benign according to our data. Variant chr3-129977111-T-C is described in ClinVar as [Benign]. Clinvar id is 260116.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-129977111-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.03 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRH	NM_007117.5 linkuse as main transcript	c.624T>C	p.Leu208Leu	synonymous_variant	3/3	ENST00000302649.4	NP_009048.1	P20396
LOC124906284	use as main transcript	n.129977111T>C		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRH	ENST00000302649.4 linkuse as main transcript	c.624T>C	p.Leu208Leu	synonymous_variant	3/3	1	NM_007117.5	ENSP00000303452.3		P20396
TRH	ENST00000507066.1 linkuse as main transcript	c.612T>C	p.Leu204Leu	synonymous_variant	3/3	5		ENSP00000426522.1		D6RFM1

Frequencies

GnomAD3 genomes

AF:

0.962

AC:

146087

AN:

151932

Hom.:

70477

Cov.:

show subpopulations

Gnomad AFR

AF:

0.870

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.981

Gnomad ASJ

AF:

0.992

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.991

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.962

GnomAD3 exomes

AF:

0.988

AC:

207976

AN:

210400

Hom.:

102920

AF XY:

0.991

AC XY:

113080

AN XY:

114120

show subpopulations

Gnomad AFR exome

AF:

0.862

Gnomad AMR exome

AF:

0.993

Gnomad ASJ exome

AF:

0.993

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.999

Gnomad OTH exome

AF:

0.993

GnomAD4 exome

AF:

0.996

AC:

1401244

AN:

1407332

Hom.:

697929

Cov.:

AF XY:

0.996

AC XY:

692487

AN XY:

695202

show subpopulations

Gnomad4 AFR exome

AF:

0.856

Gnomad4 AMR exome

AF:

0.990

Gnomad4 ASJ exome

AF:

0.994

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.989

GnomAD4 genome

AF:

0.961

AC:

146187

AN:

152050

Hom.:

70518

Cov.:

AF XY:

0.963

AC XY:

71576

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.870

Gnomad4 AMR

AF:

0.981

Gnomad4 ASJ

AF:

0.992

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.999

Gnomad4 OTH

AF:

0.962

Alfa

AF:

0.992

Hom.:

115746

Bravo

AF:

0.955

Asia WGS

AF:

0.990

AC:

3441

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Hypothalamic hypothyroidism

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

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

-0.86

CADD

Benign

0.74

DANN

Benign

0.44

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