11-118667599-G-T

Variant names:

• chr11-118667599-G-T
• rs692750
• NM_007180.3:c.90-4160C>A

Variant summary

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

The NM_007180.3(TREH):​c.90-4160C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 152,014 control chromosomes in the GnomAD database, including 8,007 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 0.32 (8007 hom., cov: 32)
• Consequence: TREH NM_007180.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54
• Publications: 9 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.449 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.90-4160C>A		intron	N/A	NP_009111.2	O43280-1
	TREH	NM_001301065.2		c.90-4160C>A		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.90-4160C>A		intron	N/A	ENSP00000264029.5	O43280-1
	TREH	ENST00000397925.2	TSL:1	c.90-4160C>A		intron	N/A	ENSP00000381020.2	O43280-2
	TREH	ENST00000854539.1		c.90-4160C>A		intron	N/A	ENSP00000524598.1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47980 AN: 151896 Hom.: 7993 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.316 AC: 48011 AN: 152014 Hom.: 8007 Cov.: 32 AF XY: 0.316 AC XY: 23489 AN XY: 74290

African (AFR) AF: 0.241 AC: 9995 AN: 41450

American (AMR) AF: 0.458 AC: 7002 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1267 AN: 3464

East Asian (EAS) AF: 0.401 AC: 2070 AN: 5164

South Asian (SAS) AF: 0.189 AC: 909 AN: 4820

European-Finnish (FIN) AF: 0.314 AC: 3312 AN: 10560

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.327 AC: 22217 AN: 67964

Other (OTH) AF: 0.330 AC: 695 AN: 2108

Alfa AF: 0.324 Hom.: 1059

Bravo AF: 0.331

Asia WGS AF: 0.268 AC: 937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.86
PhyloP100		1.5
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: rs692750; hg19: chr11-118538308;