Genetic Variant NM_007117.5: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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRH	NM_007117.5 link	c.212-102G>T		intron_variant	Intron 2 of 2	ENST00000302649.4	NP_009048.1	P20396
LOC124906284		n.129976597G>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRH	ENST00000302649.4 link	c.212-102G>T		intron_variant	Intron 2 of 2	1	NM_007117.5	ENSP00000303452.3		P20396

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

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

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 v4.3

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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NM_007117.5:c.212-102G>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over