rs723867

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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

African (AFR) AF: 0.677 AC: 7557 AN: 11166

American (AMR) AF: 0.409 AC: 4612 AN: 11280

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 4826 AN: 11394

East Asian (EAS) AF: 0.486 AC: 12770 AN: 26284

South Asian (SAS) AF: 0.247 AC: 4568 AN: 18492

European-Finnish (FIN) AF: 0.256 AC: 7940 AN: 30992

Middle Eastern (MID) AF: 0.429 AC: 755 AN: 1758

European-Non Finnish (NFE) AF: 0.257 AC: 77613 AN: 302172

Other (OTH) AF: 0.339 AC: 7533 AN: 22198

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

African (AFR) AF: 0.672 AC: 27769 AN: 41328

American (AMR) AF: 0.407 AC: 6149 AN: 15102

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1513 AN: 3444

East Asian (EAS) AF: 0.519 AC: 2665 AN: 5132

South Asian (SAS) AF: 0.254 AC: 1226 AN: 4820

European-Finnish (FIN) AF: 0.259 AC: 2735 AN: 10552

Middle Eastern (MID) AF: 0.479 AC: 140 AN: 292

European-Non Finnish (NFE) AF: 0.258 AC: 17366 AN: 67336

Other (OTH) AF: 0.391 AC: 818 AN: 2090

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
PhyloP100		-2.8
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: rs723867; hg19: chr12-72935947; COSMIC: COSV53836984;