rs723867

Variant names:

• chr12-72542167-G-C
• rs723867
• NM_013381.3:c.1723-124G>C

Variant summary

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

The NM_013381.3(TRHDE):​c.1723-124G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 586,744 control chromosomes in the GnomAD database, including 35,676 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 0.40 (14654 hom., cov: 32)
  • Exomes 𝑓: 0.29 (21022 hom.)
• Consequence: TRHDE NM_013381.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.81

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRHDE	NM_013381.3	c.1723-124G>C		intron_variant	Intron 6 of 18	ENST00000261180.10	NP_037513.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRHDE	ENST00000261180.10	c.1723-124G>C		intron_variant	Intron 6 of 18	1	NM_013381.3	ENSP00000261180.5
TRHDE	ENST00000547300.2	c.1189-124G>C		intron_variant	Intron 2 of 4	3		ENSP00000447822.2

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60436 AN: 150888 Hom.: 14611 Cov.: 32

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.474

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.386

GnomAD4 exome AF: 0.294 AC: 128174 AN: 435736 Hom.: 21022 AF XY: 0.291 AC XY: 65206 AN XY: 223782

Gnomad4 AFR exome AF: 0.677

Gnomad4 AMR exome AF: 0.409

Gnomad4 ASJ exome AF: 0.424

Gnomad4 EAS exome AF: 0.486

Gnomad4 SAS exome AF: 0.247

Gnomad4 FIN exome AF: 0.256

Gnomad4 NFE exome AF: 0.257

Gnomad4 OTH exome AF: 0.339

GnomAD4 genome AF: 0.401 AC: 60524 AN: 151008 Hom.: 14654 Cov.: 32 AF XY: 0.400 AC XY: 29470 AN XY: 73756

Gnomad4 AFR AF: 0.672

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.519

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.391

Alfa AF: 0.334 Hom.: 1306

Bravo AF: 0.431

Asia WGS AF: 0.406 AC: 1406 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.028
DANN	Benign	0.50

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: rs723867; hg19: chr12-72935947; COSMIC: COSV53836984;