chr11-118672854-C-T

Variant names:

• chr11-118672854-C-T
• rs10892251
• NM_007180.3:c.89+6685G>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.89+6685G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 151,984 control chromosomes in the GnomAD database, including 3,186 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 0.19 (3186 hom., cov: 31)
• Consequence: TREH NM_007180.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• 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=-0.59).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.341 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.89+6685G>A		intron	N/A	NP_009111.2
	TREH	NM_001301065.2		c.89+6685G>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.89+6685G>A		intron	N/A	ENSP00000264029.5
	TREH	ENST00000397925.2	TSL:1	c.89+6685G>A		intron	N/A	ENSP00000381020.2
	TREH	ENST00000527558.1	TSL:4	n.152+6685G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28991 AN: 151868 Hom.: 3183 Cov.: 31

Gnomad AFR AF: 0.0763

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.191 AC: 29002 AN: 151984 Hom.: 3186 Cov.: 31 AF XY: 0.194 AC XY: 14440 AN XY: 74284

African (AFR) AF: 0.0762 AC: 3161 AN: 41476

American (AMR) AF: 0.201 AC: 3072 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 726 AN: 3468

East Asian (EAS) AF: 0.272 AC: 1408 AN: 5170

South Asian (SAS) AF: 0.355 AC: 1710 AN: 4814

European-Finnish (FIN) AF: 0.235 AC: 2478 AN: 10532

Middle Eastern (MID) AF: 0.219 AC: 64 AN: 292

European-Non Finnish (NFE) AF: 0.233 AC: 15824 AN: 67950

Other (OTH) AF: 0.189 AC: 398 AN: 2110

Alfa AF: 0.217 Hom.: 14451

Bravo AF: 0.177

Asia WGS AF: 0.275 AC: 955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Benign	0.90
PhyloP100		0.30
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: rs10892251; hg19: chr11-118543563;