rs10784975

chr12-72586750-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.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

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRHDE	NM_013381.3	c.2321+11208G>A		intron_variant		ENST00000261180.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRHDE	ENST00000261180.10	c.2321+11208G>A		intron_variant		1	NM_013381.3	P1
TRHDE	ENST00000549138.5	n.750+11208G>A		intron_variant, non_coding_transcript_variant		5
TRHDE	ENST00000549922.1	n.217+11208G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.680

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.577

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.402

Alfa AF: 0.346 Hom.: 1837

Bravo AF: 0.435

Asia WGS AF: 0.430 AC: 1498 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.0050
Dann	Benign	0.68

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: rs10784975; hg19: chr12-72980530;