rs514912

Variant names:

• chr12-72484216-G-A
• rs514912
• NM_013381.3:c.1584+11036G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013381.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRHDE	NM_013381.3	MANE Select	c.1584+11036G>A		intron	N/A	NP_037513.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRHDE	ENST00000261180.10	TSL:1 MANE Select	c.1584+11036G>A		intron	N/A	ENSP00000261180.5
	TRHDE	ENST00000547300.2	TSL:3	c.1189-58075G>A		intron	N/A	ENSP00000447822.2

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

African (AFR) AF: 0.0825 AC: 3429 AN: 41540

American (AMR) AF: 0.274 AC: 4192 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 724 AN: 3472

East Asian (EAS) AF: 0.498 AC: 2564 AN: 5150

South Asian (SAS) AF: 0.230 AC: 1112 AN: 4828

European-Finnish (FIN) AF: 0.240 AC: 2526 AN: 10542

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.167 AC: 11344 AN: 67946

Other (OTH) AF: 0.192 AC: 406 AN: 2112

Alfa AF: 0.171 Hom.: 3714

Bravo AF: 0.177

Asia WGS AF: 0.346 AC: 1202 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.64
DANN	Benign	0.18
PhyloP100		-0.14
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: rs514912; hg19: chr12-72877996;