rs2367895

chr12-72227415-C-A

Variant summary

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

The XM_017019244.2(TRHDE):c.-130-59266C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 151,934 control chromosomes in the GnomAD database, including 17,708 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 0.48 (17708 hom., cov: 31)
• Consequence: TRHDE XM_017019244.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

Genes affected

TRHDE (HGNC:30748): (thyrotropin releasing hormone degrading enzyme) This gene encodes a member of the peptidase M1 family. The encoded protein is an extracellular peptidase that specifically cleaves and inactivates the neuropeptide thyrotropin-releasing hormone.[provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRHDE	XM_017019244.2	c.-130-59266C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRHDE	ENST00000548156.1	n.279+121663C>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72744 AN: 151814 Hom.: 17679 Cov.: 31

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.479 AC: 72817 AN: 151934 Hom.: 17708 Cov.: 31 AF XY: 0.482 AC XY: 35803 AN XY: 74246

Gnomad4 AFR AF: 0.440

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.424

Gnomad4 EAS AF: 0.417

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.511

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.494

Alfa AF: 0.484 Hom.: 3264

Bravo AF: 0.475

Asia WGS AF: 0.542 AC: 1886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	9.6
Dann	Benign	0.87

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2367895; hg19: chr12-72621195;