rs2044305

Positions:

• chr12-72352118-G-A
• chr12-72352118-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.1189-25877G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 151,558 control chromosomes in the GnomAD database, including 8,627 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 0.33 (8627 hom., cov: 32)
• Consequence: TRHDE NM_013381.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRHDE	NM_013381.3	c.1189-25877G>A		intron_variant		ENST00000261180.10
TRHDE	XM_005268819.6	c.1189-25877G>A		intron_variant
TRHDE	XM_017019243.3	c.1189-25877G>A		intron_variant
TRHDE	XM_017019244.2	c.145-25877G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRHDE	ENST00000261180.10	c.1189-25877G>A		intron_variant		1	NM_013381.3	P1
TRHDE	ENST00000547300.2	c.1188+65164G>A		intron_variant		3
TRHDE	ENST00000548156.1	n.280-25877G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49329 AN: 151438 Hom.: 8611 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.326 AC: 49372 AN: 151558 Hom.: 8627 Cov.: 32 AF XY: 0.330 AC XY: 24428 AN XY: 74054

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.310

Alfa AF: 0.355 Hom.: 17948

Bravo AF: 0.313

Asia WGS AF: 0.305 AC: 1055 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.72
DANN	Benign	0.53

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: rs2044305; hg19: chr12-72745898;