rs2367895

Variant names:

• chr12-72227415-C-A
• rs2367895
• ENST00000548156.1:n.279+121663C>A

Variant summary

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

The ENST00000548156.1(TRHDE):​n.279+121663C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 151,934 control chromosomes in the GnomAD database, including 17,708 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 0.48 (17708 hom., cov: 31)
• Consequence: TRHDE ENST00000548156.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• 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=-0.7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRHDE	XM_017019244.2	c.-130-59266C>A		intron_variant	Intron 2 of 19		XP_016874733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRHDE	ENST00000548156.1	n.279+121663C>A		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72744 AN: 151814 Hom.: 17679 Cov.: 31

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.479 AC: 72817 AN: 151934 Hom.: 17708 Cov.: 31 AF XY: 0.482 AC XY: 35803 AN XY: 74246

African (AFR) AF: 0.440 AC: 18231 AN: 41448

American (AMR) AF: 0.522 AC: 7967 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1470 AN: 3470

East Asian (EAS) AF: 0.417 AC: 2141 AN: 5138

South Asian (SAS) AF: 0.618 AC: 2972 AN: 4808

European-Finnish (FIN) AF: 0.511 AC: 5392 AN: 10548

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.485 AC: 32958 AN: 67952

Other (OTH) AF: 0.494 AC: 1042 AN: 2108

Alfa AF: 0.477 Hom.: 5870

Bravo AF: 0.475

Asia WGS AF: 0.542 AC: 1886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.6
DANN	Benign	0.87
PhyloP100		0.30

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2367895; hg19: chr12-72621195;