Menu
GeneBe

rs5660

chr3-129976871-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars. Variant chr3-129976871-T-C is described in Lovd as [Benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.978 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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
TRHNM_007117.5 linkuse as main transcriptc.384T>C p.Asp128= synonymous_variant 3/3 ENST00000302649.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TRHENST00000302649.4 linkuse as main transcriptc.384T>C p.Asp128= synonymous_variant 3/31 NM_007117.5 P2
TRHENST00000507066.1 linkuse as main transcriptc.372T>C p.Asp124= synonymous_variant 3/35 A1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0717
AC:
10755
AN:
150098
Hom.:
445
Cov.:
30
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.:
98
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0716
AC:
10762
AN:
150224
Hom.:
445
Cov.:
30
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:
66
AN:
3478
EpiCase
AF:
0.0775
EpiControl
AF:
0.0809

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -

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.

Other links and lift over

dbSNP: rs5660; hg19: chr3-129695714; COSMIC: COSV57014970; API