12-72586750-G-A

Variant names:

• chr12-72586750-G-A
• rs10784975
• NM_013381.3:c.2321+11208G>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.2321+11208G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 149,344 control chromosomes in the GnomAD database, including 14,812 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 0.41 (14812 hom., cov: 27)
• Consequence: TRHDE NM_013381.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.673 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRHDE	NM_013381.3	MANE Select	c.2321+11208G>A		intron	N/A	NP_037513.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRHDE	ENST00000261180.10	TSL:1 MANE Select	c.2321+11208G>A		intron	N/A	ENSP00000261180.5
	TRHDE	ENST00000549138.5	TSL:5	n.750+11208G>A		intron	N/A
	TRHDE	ENST00000549922.1	TSL:3	n.217+11208G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.406 AC: 60539 AN: 149226 Hom.: 14771 Cov.: 27

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.406 AC: 60624 AN: 149344 Hom.: 14812 Cov.: 27 AF XY: 0.407 AC XY: 29500 AN XY: 72570

African (AFR) AF: 0.680 AC: 27687 AN: 40716

American (AMR) AF: 0.411 AC: 6158 AN: 14994

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1501 AN: 3450

East Asian (EAS) AF: 0.577 AC: 2915 AN: 5054

South Asian (SAS) AF: 0.250 AC: 1178 AN: 4710

European-Finnish (FIN) AF: 0.268 AC: 2626 AN: 9788

Middle Eastern (MID) AF: 0.497 AC: 143 AN: 288

European-Non Finnish (NFE) AF: 0.259 AC: 17447 AN: 67390

Other (OTH) AF: 0.402 AC: 827 AN: 2058

Alfa AF: 0.355 Hom.: 2014

Bravo AF: 0.435

Asia WGS AF: 0.430 AC: 1498 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0050
DANN	Benign	0.68
PhyloP100		-1.7
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: rs10784975; hg19: chr12-72980530;