rs16892496

chr8-109097622-A-Cchr8-109097622-A-Gchr8-109097622-A-T

Variant summary

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

The NM_003301.7(TRHR):c.789+9321A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,066 control chromosomes in the GnomAD database, including 7,869 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 0.31 (7869 hom., cov: 32)
• Consequence: TRHR NM_003301.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRHR	NM_003301.7	c.789+9321A>C		intron_variant		ENST00000518632.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRHR	ENST00000518632.2	c.789+9321A>C		intron_variant		5	NM_003301.7	P1
TRHR	ENST00000311762.2	c.789+9321A>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47364 AN: 151948 Hom.: 7852 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.312 AC: 47414 AN: 152066 Hom.: 7869 Cov.: 32 AF XY: 0.318 AC XY: 23630 AN XY: 74350

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.309

Alfa AF: 0.260 Hom.: 1454

Bravo AF: 0.317

Asia WGS AF: 0.487 AC: 1691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.69
Dann	Benign	0.53

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: rs16892496; hg19: chr8-110109851;