rs7832552

Variant names:

• chr8-109103447-C-T
• rs7832552
• NM_003301.7:c.789+15146C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003301.7(TRHR):​c.789+15146C>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 151,962 control chromosomes in the GnomAD database, including 7,364 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 0.30 (7364 hom., cov: 32)
• Consequence: TRHR NM_003301.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.974
• Publications: 57 publications found

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]

TRHR Gene-Disease associations (from GenCC):

• hypothyroidism, congenital, nongoitrous, 7

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• resistance to thyrotropin-releasing hormone syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRHR	NM_003301.7	c.789+15146C>T		intron_variant	Intron 2 of 2	ENST00000518632.2	NP_003292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRHR	ENST00000518632.2	c.789+15146C>T		intron_variant	Intron 2 of 2	5	NM_003301.7	ENSP00000430711.2
TRHR	ENST00000311762.2	c.789+15146C>T		intron_variant	Intron 1 of 1	1		ENSP00000309818.2

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45403 AN: 151844 Hom.: 7350 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.299 AC: 45440 AN: 151962 Hom.: 7364 Cov.: 32 AF XY: 0.304 AC XY: 22614 AN XY: 74286

African (AFR) AF: 0.192 AC: 7952 AN: 41448

American (AMR) AF: 0.437 AC: 6666 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 751 AN: 3468

East Asian (EAS) AF: 0.473 AC: 2436 AN: 5154

South Asian (SAS) AF: 0.401 AC: 1934 AN: 4824

European-Finnish (FIN) AF: 0.326 AC: 3439 AN: 10558

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21108 AN: 67950

Other (OTH) AF: 0.296 AC: 624 AN: 2110

Alfa AF: 0.308 Hom.: 30958

Bravo AF: 0.303

Asia WGS AF: 0.450 AC: 1565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.97
DANN	Benign	0.50
PhyloP100		-0.97
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7832552; hg19: chr8-110115676;