rs61740106
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_007117.5(TRH):c.248G>A(p.Arg83His) variant causes a missense change. The variant allele was found at a frequency of 0.00199 in 1,613,804 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0092 ( 22 hom., cov: 31)
Exomes 𝑓: 0.0012 ( 23 hom. )
Consequence
TRH
NM_007117.5 missense
NM_007117.5 missense
Scores
8
6
4
Clinical Significance
Conservation
PhyloP100: 5.04
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.01296562).
BP6
?
Variant 3-129976735-G-A is Benign according to our data. Variant chr3-129976735-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 445972.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-129976735-G-A is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00923 (1403/152052) while in subpopulation AFR AF= 0.0298 (1235/41454). AF 95% confidence interval is 0.0284. There are 22 homozygotes in gnomad4. There are 642 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 22 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRH | NM_007117.5 | c.248G>A | p.Arg83His | missense_variant | 3/3 | ENST00000302649.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRH | ENST00000302649.4 | c.248G>A | p.Arg83His | missense_variant | 3/3 | 1 | NM_007117.5 | P2 | |
TRH | ENST00000507066.1 | c.236G>A | p.Arg79His | missense_variant | 3/3 | 5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00920 AC: 1398AN: 151934Hom.: 22 Cov.: 31
GnomAD3 genomes
?
AF:
AC:
1398
AN:
151934
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00270 AC: 678AN: 251276Hom.: 8 AF XY: 0.00237 AC XY: 322AN XY: 135804
GnomAD3 exomes
AF:
AC:
678
AN:
251276
Hom.:
AF XY:
AC XY:
322
AN XY:
135804
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00124 AC: 1811AN: 1461752Hom.: 23 Cov.: 94 AF XY: 0.00115 AC XY: 836AN XY: 727170
GnomAD4 exome
AF:
AC:
1811
AN:
1461752
Hom.:
Cov.:
94
AF XY:
AC XY:
836
AN XY:
727170
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00923 AC: 1403AN: 152052Hom.: 22 Cov.: 31 AF XY: 0.00864 AC XY: 642AN XY: 74336
GnomAD4 genome
?
AF:
AC:
1403
AN:
152052
Hom.:
Cov.:
31
AF XY:
AC XY:
642
AN XY:
74336
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
1
ALSPAC
AF:
AC:
3
ESP6500AA
AF:
AC:
136
ESP6500EA
AF:
AC:
7
ExAC
?
AF:
AC:
392
Asia WGS
AF:
AC:
9
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Feb 20, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 20, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at