rs7829028

Variant names:

• chr8-109097301-C-T
• rs7829028
• NM_003301.7:c.789+9000C>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+9000C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,018 control chromosomes in the GnomAD database, including 5,753 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 0.21 (5753 hom., cov: 32)
• Consequence: TRHR NM_003301.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.372
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRHR	NM_003301.7	c.789+9000C>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+9000C>T		intron_variant	Intron 2 of 2	5	NM_003301.7	ENSP00000430711.2
TRHR	ENST00000311762.2	c.789+9000C>T		intron_variant	Intron 1 of 1	1		ENSP00000309818.2

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32108 AN: 151900 Hom.: 5718 Cov.: 32

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.0453

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0828

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.212 AC: 32195 AN: 152018 Hom.: 5753 Cov.: 32 AF XY: 0.210 AC XY: 15581 AN XY: 74304

African (AFR) AF: 0.488 AC: 20210 AN: 41402

American (AMR) AF: 0.141 AC: 2158 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 479 AN: 3468

East Asian (EAS) AF: 0.0449 AC: 232 AN: 5172

South Asian (SAS) AF: 0.139 AC: 671 AN: 4818

European-Finnish (FIN) AF: 0.0828 AC: 876 AN: 10584

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 7034 AN: 67976

Other (OTH) AF: 0.205 AC: 433 AN: 2112

Alfa AF: 0.165 Hom.: 621

Bravo AF: 0.228

Asia WGS AF: 0.144 AC: 504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.5
DANN	Benign	0.31
PhyloP100		0.37
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: rs7829028; hg19: chr8-110109530;