rs17783131

Positions:

• chr12-72326012-A-C
• chr12-72326012-A-T

Variant summary

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

The ENST00000261180.10(TRHDE):​c.1188+39058A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,036 control chromosomes in the GnomAD database, including 9,961 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 0.35 (9961 hom., cov: 32)
• Consequence: TRHDE ENST00000261180.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480

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 (NFE) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRHDE	NM_013381.3	c.1188+39058A>C		intron_variant		ENST00000261180.10	NP_037513.2
TRHDE	XM_005268819.6	c.1188+39058A>C		intron_variant			XP_005268876.3
TRHDE	XM_017019243.3	c.1188+39058A>C		intron_variant			XP_016874732.3
TRHDE	XM_017019244.2	c.144+39058A>C		intron_variant			XP_016874733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRHDE	ENST00000261180.10	c.1188+39058A>C		intron_variant		1	NM_013381.3	ENSP00000261180	P1
TRHDE	ENST00000547300.2	c.1188+39058A>C		intron_variant		3		ENSP00000447822
TRHDE	ENST00000548156.1	n.280-51983A>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53060 AN: 151916 Hom.: 9965 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.0915

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.349 AC: 53061 AN: 152036 Hom.: 9961 Cov.: 32 AF XY: 0.346 AC XY: 25737 AN XY: 74322

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.0917

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.351

Alfa AF: 0.370 Hom.: 1848

Bravo AF: 0.330

Asia WGS AF: 0.275 AC: 957 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	1.5
DANN	Benign	0.75

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: rs17783131; hg19: chr12-72719792;