rs13097335

Positions:

• chr3-129976597-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.656

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]

LOC124906284 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TRH	NM_007117.5	c.212-102G>T		intron_variant		ENST00000302649.4	NP_009048.1
LOC124906284		n.129976597G>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRH	ENST00000302649.4	c.212-102G>T		intron_variant		1	NM_007117.5	ENSP00000303452.3
TRH	ENST00000507066.1	c.200-102G>T		intron_variant		5		ENSP00000426522.1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38484 AN: 151880 Hom.: 5380 Cov.: 32

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

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.204

Gnomad4 ASJ exome AF: 0.266

Gnomad4 EAS exome AF: 0.300

Gnomad4 SAS exome AF: 0.346

Gnomad4 FIN exome AF: 0.346

Gnomad4 NFE exome AF: 0.311

Gnomad4 OTH exome AF: 0.289

GnomAD4 genome AF: 0.253 AC: 38481 AN: 151998 Hom.: 5379 Cov.: 32 AF XY: 0.255 AC XY: 18910 AN XY: 74262

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.258

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.366

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.236

Alfa AF: 0.272 Hom.: 731

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
DANN	Benign	0.65

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

Other links and lift over

dbSNP: rs13097335; hg19: chr3-129695440;