12-72549272-G-C

Position:

• chr12-72549272-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013381.3(TRHDE):​c.1788+6916G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 151,660 control chromosomes in the GnomAD database, including 26,268 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 0.53 (26268 hom., cov: 33)
• Consequence: TRHDE NM_013381.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRHDE	NM_013381.3	c.1788+6916G>C		intron_variant		ENST00000261180.10	NP_037513.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRHDE	ENST00000261180.10	c.1788+6916G>C		intron_variant		1	NM_013381.3	ENSP00000261180.5
TRHDE	ENST00000547300.2	c.1254+6916G>C		intron_variant		3		ENSP00000447822.2

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81074 AN: 151542 Hom.: 26260 Cov.: 33

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.724

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.535 AC: 81079 AN: 151660 Hom.: 26268 Cov.: 33 AF XY: 0.538 AC XY: 39842 AN XY: 74124

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.564

Gnomad4 ASJ AF: 0.544

Gnomad4 EAS AF: 0.481

Gnomad4 SAS AF: 0.725

Gnomad4 FIN AF: 0.705

Gnomad4 NFE AF: 0.719

Gnomad4 OTH AF: 0.561

Alfa AF: 0.613 Hom.: 3832

Bravo AF: 0.500

Asia WGS AF: 0.556 AC: 1930 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.1
DANN	Benign	0.40

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: rs1214897; hg19: chr12-72943052;