dbSNP rs13097335: TRH:c.212-102G>T (chr3-129976597-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007117.5(TRH):c.212-102G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 1,336,162 control chromosomes in the GnomAD database, including 62,027 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5379 hom., cov: 32)

Exomes 𝑓: 0.31 ( 56648 hom. )

Consequence

TRH
NM_007117.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.656

Publications

1 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007117.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRH	NM_007117.5	MANE Select	c.212-102G>T		intron	N/A	NP_009048.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TRH	ENST00000302649.4	TSL:1 MANE Select	c.212-102G>T	intron	N/A	ENSP00000303452.3
TRH	ENST00000507066.1	TSL:5	c.200-102G>T	intron	N/A	ENSP00000426522.1
ENSG00000250643	ENST00000785099.1		n.298-4489C>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.253

AC:

38484

AN:

151880

Hom.:

5380

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.469

Gnomad AMR

AF:

0.197

Gnomad ASJ

AF:

0.258

Gnomad EAS

AF:

0.253

Gnomad SAS

AF:

0.353

Gnomad FIN

AF:

0.366

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.303

Gnomad OTH

AF:

0.237

GnomAD4 exome

AF:

0.305

AC:

361406

AN:

1184164

Hom.:

56648

AF XY:

0.306

AC XY:

180530

AN XY:

589776

show subpopulations

African (AFR)

AF:

0.138

AC:

3730

AN:

26964

American (AMR)

AF:

0.204

AC:

6217

AN:

30452

Ashkenazi Jewish (ASJ)

AF:

0.266

AC:

5079

AN:

19106

East Asian (EAS)

AF:

0.300

AC:

11435

AN:

38142

South Asian (SAS)

AF:

0.346

AC:

23031

AN:

66616

European-Finnish (FIN)

AF:

0.346

AC:

13359

AN:

38628

Middle Eastern (MID)

AF:

0.229

AC:

787

AN:

3444

European-Non Finnish (NFE)

AF:

0.311

AC:

283190

AN:

910388

Other (OTH)

AF:

0.289

AC:

14578

AN:

50424

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

12804

25608

38411

51215

64019

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9056

18112

27168

36224

45280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.253

AC:

38481

AN:

151998

Hom.:

5379

Cov.:

AF XY:

0.255

AC XY:

18910

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.149

AC:

6178

AN:

41488

American (AMR)

AF:

0.197

AC:

3020

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.258

AC:

894

AN:

3470

East Asian (EAS)

AF:

0.252

AC:

1290

AN:

5116

South Asian (SAS)

AF:

0.353

AC:

1700

AN:

4810

European-Finnish (FIN)

AF:

0.366

AC:

3869

AN:

10566

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.302

AC:

20550

AN:

67938

Other (OTH)

AF:

0.236

AC:

499

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1413

2826

4240

5653

7066

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

406

812

1218

1624

2030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.267

Hom.:

742

Bravo

AF:

0.232

Asia WGS

AF:

0.306

AC:

1063

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.6

(source)

DANN

Benign

0.65

PhyloP100

-0.66

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over