chr11-118667478-G-T

Variant names:

• chr11-118667478-G-T
• rs607527
• NM_007180.3:c.90-4039C>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.90-4039C>A 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 152,142 control chromosomes in the GnomAD database, including 9,575 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 (9575 hom., cov: 33)
• Consequence: TREH NM_007180.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.25
• Publications: 15 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=-1.1).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.467 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TREH	NM_007180.3	MANE Select	c.90-4039C>A		intron	N/A	NP_009111.2
	TREH	NM_001301065.2		c.90-4039C>A		intron	N/A	NP_001287994.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TREH	ENST00000264029.9	TSL:1 MANE Select	c.90-4039C>A		intron	N/A	ENSP00000264029.5
	TREH	ENST00000397925.2	TSL:1	c.90-4039C>A		intron	N/A	ENSP00000381020.2
	TREH	ENST00000527558.1	TSL:4	n.153-4282C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53021 AN: 152024 Hom.: 9553 Cov.: 33

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.483

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.354

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: 0.349 AC: 53086 AN: 152142 Hom.: 9575 Cov.: 33 AF XY: 0.348 AC XY: 25871 AN XY: 74378

African (AFR) AF: 0.339 AC: 14064 AN: 41484

American (AMR) AF: 0.476 AC: 7278 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1274 AN: 3470

East Asian (EAS) AF: 0.446 AC: 2312 AN: 5184

South Asian (SAS) AF: 0.197 AC: 948 AN: 4822

European-Finnish (FIN) AF: 0.315 AC: 3335 AN: 10584

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

European-Non Finnish (NFE) AF: 0.332 AC: 22585 AN: 67992

Other (OTH) AF: 0.353 AC: 745 AN: 2112

Alfa AF: 0.334 Hom.: 8747

Bravo AF: 0.368

Asia WGS AF: 0.305 AC: 1062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.050
DANN	Benign	0.25
PhyloP100		-3.3
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: rs607527; hg19: chr11-118538187;