rs507080

Variant names:

• chr11-118678873-G-A
• rs507080
• NM_007180.3:c.89+666C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007180.3(TREH):​c.89+666C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 151,992 control chromosomes in the GnomAD database, including 9,619 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 (9619 hom., cov: 31)
• Consequence: TREH NM_007180.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.963
• Publications: 20 publications found

Genes affected

TREH (HGNC:12266): (trehalase) This gene encodes an enzyme that hydrolyses trehalose, a disaccharide formed from two glucose molecules found mainly in fungi, plants, and insects. A partial duplication of this gene is located adjacent to this locus on chromosome 11. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

TREH Gene-Disease associations (from GenCC):

• diarrhea-vomiting due to trehalase deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TREH	NM_007180.3	c.89+666C>T		intron_variant	Intron 1 of 14	ENST00000264029.9	NP_009111.2
TREH	NM_001301065.2	c.89+666C>T		intron_variant	Intron 1 of 13		NP_001287994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TREH	ENST00000264029.9	c.89+666C>T		intron_variant	Intron 1 of 14	1	NM_007180.3	ENSP00000264029.5

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53126 AN: 151874 Hom.: 9597 Cov.: 31

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.483

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.350 AC: 53192 AN: 151992 Hom.: 9619 Cov.: 31 AF XY: 0.349 AC XY: 25900 AN XY: 74290

African (AFR) AF: 0.343 AC: 14198 AN: 41444

American (AMR) AF: 0.476 AC: 7274 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1274 AN: 3468

East Asian (EAS) AF: 0.445 AC: 2296 AN: 5164

South Asian (SAS) AF: 0.197 AC: 950 AN: 4824

European-Finnish (FIN) AF: 0.314 AC: 3311 AN: 10552

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22597 AN: 67966

Other (OTH) AF: 0.354 AC: 745 AN: 2106

Alfa AF: 0.351 Hom.: 1237

Bravo AF: 0.369

Asia WGS AF: 0.305 AC: 1063 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.5
DANN	Benign	0.56
PhyloP100		0.96
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs507080; hg19: chr11-118549582;