rs7645772

Variant names:

• chr3-129976530-T-C
• rs7645772
• NM_007117.5:c.212-169T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-129976530-T-C
• chr3-129976530-T-G

Variant summary

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

The NM_007117.5(TRH):​c.212-169T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 152,050 control chromosomes in the GnomAD database, including 11,344 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 0.36 (11344 hom., cov: 33)
• Consequence: TRH NM_007117.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.408
• Publications: 6 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRH	NM_007117.5	c.212-169T>C		intron_variant	Intron 2 of 2	ENST00000302649.4	NP_009048.1
LOC124906284		n.129976530T>C		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRH	ENST00000302649.4	c.212-169T>C		intron_variant	Intron 2 of 2	1	NM_007117.5	ENSP00000303452.3

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53995 AN: 151932 Hom.: 11351 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.355 AC: 53987 AN: 152050 Hom.: 11344 Cov.: 33 AF XY: 0.354 AC XY: 26335 AN XY: 74300

African (AFR) AF: 0.126 AC: 5224 AN: 41504

American (AMR) AF: 0.355 AC: 5426 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1842 AN: 3466

East Asian (EAS) AF: 0.223 AC: 1146 AN: 5132

South Asian (SAS) AF: 0.381 AC: 1835 AN: 4818

European-Finnish (FIN) AF: 0.452 AC: 4790 AN: 10586

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.476 AC: 32353 AN: 67948

Other (OTH) AF: 0.379 AC: 799 AN: 2110

Alfa AF: 0.440 Hom.: 25515

Bravo AF: 0.340

Asia WGS AF: 0.245 AC: 852 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	3.7
DANN	Benign	0.41
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7645772; hg19: chr3-129695373; COSMIC: COSV107311353;