rs3925087

Positions:

• chr8-109110449-T-C
• chr8-109110449-T-G

Variant summary

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

The NM_003301.7(TRHR):​c.790-8599T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 151,816 control chromosomes in the GnomAD database, including 12,305 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 0.40 (12305 hom., cov: 31)
• Consequence: TRHR NM_003301.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.838

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRHR	NM_003301.7	c.790-8599T>C		intron_variant		ENST00000518632.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRHR	ENST00000518632.2	c.790-8599T>C		intron_variant		5	NM_003301.7	P1
TRHR	ENST00000311762.2	c.790-8599T>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60413 AN: 151698 Hom.: 12289 Cov.: 31

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.393

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.398 AC: 60486 AN: 151816 Hom.: 12305 Cov.: 31 AF XY: 0.403 AC XY: 29915 AN XY: 74164

Gnomad4 AFR AF: 0.429

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.395

Alfa AF: 0.297 Hom.: 1118

Bravo AF: 0.408

Asia WGS AF: 0.515 AC: 1791 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.4
DANN	Benign	0.51

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: rs3925087; hg19: chr8-110122678;