chr12-72612127-A-G

Variant names:

• chr12-72612127-A-G
• rs3852549
• NM_013381.3:c.2322-6764A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013381.3(TRHDE):​c.2322-6764A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 151,884 control chromosomes in the GnomAD database, including 16,682 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 0.43 (16682 hom., cov: 31)
• Consequence: TRHDE NM_013381.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700
• Publications: 3 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.711 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.2322-6764A>G		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.2322-6764A>G		intron	N/A	ENSP00000261180.5
	TRHDE	ENST00000549138.5	TSL:5	n.751-6764A>G		intron	N/A
	TRHDE	ENST00000549922.1	TSL:3	n.218-6764A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64756 AN: 151766 Hom.: 16625 Cov.: 31

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.401

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

GnomAD4 genome AF: 0.427 AC: 64856 AN: 151884 Hom.: 16682 Cov.: 31 AF XY: 0.426 AC XY: 31657 AN XY: 74240

African (AFR) AF: 0.718 AC: 29747 AN: 41432

American (AMR) AF: 0.417 AC: 6362 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1522 AN: 3468

East Asian (EAS) AF: 0.577 AC: 2965 AN: 5140

South Asian (SAS) AF: 0.261 AC: 1257 AN: 4812

European-Finnish (FIN) AF: 0.294 AC: 3099 AN: 10548

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18663 AN: 67926

Other (OTH) AF: 0.406 AC: 851 AN: 2098

Alfa AF: 0.327 Hom.: 11474

Bravo AF: 0.457

Asia WGS AF: 0.439 AC: 1531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.1
DANN	Benign	0.54
PhyloP100		-0.0070
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: rs3852549; hg19: chr12-73005907;