rs7955732

chr12-72331215-G-T

Variant summary

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

The NM_013381.3(TRHDE):c.1188+44261G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,068 control chromosomes in the GnomAD database, including 9,644 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 0.34 (9644 hom., cov: 32)
• Consequence: TRHDE NM_013381.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.507

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRHDE	NM_013381.3	c.1188+44261G>T		intron_variant		ENST00000261180.10
TRHDE	XM_005268819.6	c.1188+44261G>T		intron_variant
TRHDE	XM_017019243.3	c.1188+44261G>T		intron_variant
TRHDE	XM_017019244.2	c.144+44261G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRHDE	ENST00000261180.10	c.1188+44261G>T		intron_variant		1	NM_013381.3	P1
TRHDE	ENST00000547300.2	c.1188+44261G>T		intron_variant		3
TRHDE	ENST00000548156.1	n.280-46780G>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52196 AN: 151950 Hom.: 9648 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.0885

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.343 AC: 52191 AN: 152068 Hom.: 9644 Cov.: 32 AF XY: 0.340 AC XY: 25250 AN XY: 74320

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.0885

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.344

Alfa AF: 0.365 Hom.: 1812

Bravo AF: 0.325

Asia WGS AF: 0.260 AC: 905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.17
Dann	Benign	0.43

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: rs7955732; hg19: chr12-72724995;