rs514912

chr12-72484216-G-A

Variant summary

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

The NM_013381.3(TRHDE):c.1584+11036G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,070 control chromosomes in the GnomAD database, including 2,975 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 0.17 (2975 hom., cov: 32)
• Consequence: TRHDE NM_013381.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRHDE	NM_013381.3	c.1584+11036G>A		intron_variant		ENST00000261180.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRHDE	ENST00000261180.10	c.1584+11036G>A		intron_variant		1	NM_013381.3	P1
TRHDE	ENST00000547300.2	c.1189-58075G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26451 AN: 151952 Hom.: 2969 Cov.: 32

Gnomad AFR AF: 0.0826

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.174 AC: 26462 AN: 152070 Hom.: 2975 Cov.: 32 AF XY: 0.181 AC XY: 13482 AN XY: 74314

Gnomad4 AFR AF: 0.0825

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.192

Alfa AF: 0.177 Hom.: 2746

Bravo AF: 0.177

Asia WGS AF: 0.346 AC: 1202 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.64
Dann	Benign	0.18

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: rs514912; hg19: chr12-72877996;