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GeneBe

8-109119407-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_003301.7(TRHR):c.1149T>C(p.Ser383=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00066 in 1,612,420 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00040 ( 4 hom. )

Consequence

TRHR
NM_003301.7 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.324
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 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=-0.57).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-109119407-T-C is Benign according to our data. Variant chr8-109119407-T-C is described in ClinVar as [Benign]. Clinvar id is 724151.Status of the report is criteria_provided_single_submitter, 1 stars.
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=0.324 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TRHRNM_003301.7 linkuse as main transcriptc.1149T>C p.Ser383= synonymous_variant 3/3 ENST00000518632.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TRHRENST00000518632.2 linkuse as main transcriptc.1149T>C p.Ser383= synonymous_variant 3/35 NM_003301.7 P1
TRHRENST00000311762.2 linkuse as main transcriptc.1149T>C p.Ser383= synonymous_variant 2/21 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00315
AC:
479
AN:
151834
Hom.:
3
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0107
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00158
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000295
Gnomad OTH
AF:
0.00431
GnomAD3 exomes
AF:
0.000912
AC:
228
AN:
249960
Hom.:
0
AF XY:
0.000688
AC XY:
93
AN XY:
135104
show subpopulations
Gnomad AFR exome
AF:
0.0116
Gnomad AMR exome
AF:
0.000639
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000106
Gnomad OTH exome
AF:
0.000986
GnomAD4 exome
AF:
0.000398
AC:
581
AN:
1460468
Hom.:
4
Cov.:
31
AF XY:
0.000359
AC XY:
261
AN XY:
726542
show subpopulations
Gnomad4 AFR exome
AF:
0.0108
Gnomad4 AMR exome
AF:
0.000785
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000702
Gnomad4 OTH exome
AF:
0.00141
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00319
AC:
484
AN:
151952
Hom.:
3
Cov.:
32
AF XY:
0.00314
AC XY:
233
AN XY:
74254
show subpopulations
Gnomad4 AFR
AF:
0.0108
Gnomad4 AMR
AF:
0.00158
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000295
Gnomad4 OTH
AF:
0.00427
Alfa
AF:
0.00141
Hom.:
1
Bravo
AF:
0.00346
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.0000546
EpiControl
AF:
0.000356

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.57
Cadd
Benign
6.5
Dann
Benign
0.68

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: rs5776; hg19: chr8-110131636; API