NM_007180.3:c.89+789C>T

Variant names:

• chr11-118678750-G-A
• rs647878
• NM_007180.3:c.89+789C>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+789C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 150,368 control chromosomes in the GnomAD database, including 8,938 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 (8938 hom., cov: 27)
• Consequence: TREH NM_007180.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570
• Publications: 7 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 = 0.465 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007180.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TREH	NM_007180.3	MANE Select	c.89+789C>T		intron	N/A	NP_009111.2	O43280-1
	TREH	NM_001301065.2		c.89+789C>T		intron	N/A	NP_001287994.1	O43280-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TREH	ENST00000264029.9	TSL:1 MANE Select	c.89+789C>T		intron	N/A	ENSP00000264029.5	O43280-1
	TREH	ENST00000397925.2	TSL:1	c.89+789C>T		intron	N/A	ENSP00000381020.2	O43280-2
	TREH	ENST00000854539.1		c.89+789C>T		intron	N/A	ENSP00000524598.1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 51844 AN: 150254 Hom.: 8920 Cov.: 27

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.359

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.345 AC: 51903 AN: 150368 Hom.: 8938 Cov.: 27 AF XY: 0.344 AC XY: 25246 AN XY: 73372

African (AFR) AF: 0.328 AC: 13346 AN: 40736

American (AMR) AF: 0.474 AC: 7117 AN: 15022

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1269 AN: 3460

East Asian (EAS) AF: 0.444 AC: 2282 AN: 5136

South Asian (SAS) AF: 0.194 AC: 920 AN: 4734

European-Finnish (FIN) AF: 0.312 AC: 3224 AN: 10342

Middle Eastern (MID) AF: 0.370 AC: 108 AN: 292

European-Non Finnish (NFE) AF: 0.332 AC: 22474 AN: 67680

Other (OTH) AF: 0.353 AC: 730 AN: 2066

Alfa AF: 0.352 Hom.: 1043

Bravo AF: 0.366

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.46
PhyloP100		-0.057
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs647878; hg19: chr11-118549459;