11-118658418-G-A

Variant names:

• chr11-118658418-G-A
• rs7928371
• NM_007180.3:c.1623C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_007180.3(TREH):​c.1623C>T​(p.Gly541Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,610,474 control chromosomes in the GnomAD database, including 42,605 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.20 (3312 hom., cov: 33)
  • Exomes 𝑓: 0.23 (39293 hom.)
• Consequence: TREH NM_007180.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.05
• Publications: 24 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 11-118658418-G-A is Benign according to our data. Variant chr11-118658418-G-A is described in ClinVar as Benign. ClinVar VariationId is 3060997.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TREH	NM_007180.3	c.1623C>T	p.Gly541Gly	synonymous_variant	Exon 15 of 15	ENST00000264029.9	NP_009111.2
TREH	NM_001301065.2	c.1530C>T	p.Gly510Gly	synonymous_variant	Exon 14 of 14		NP_001287994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TREH	ENST00000264029.9	c.1623C>T	p.Gly541Gly	synonymous_variant	Exon 15 of 15	1	NM_007180.3	ENSP00000264029.5
TREH	ENST00000397925.2	c.1530C>T	p.Gly510Gly	synonymous_variant	Exon 14 of 14	1		ENSP00000381020.2
TREH	ENST00000613915.4	n.*1400C>T		non_coding_transcript_exon_variant	Exon 13 of 13	2		ENSP00000477923.1
TREH	ENST00000613915.4	n.*1400C>T		3_prime_UTR_variant	Exon 13 of 13	2		ENSP00000477923.1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30801 AN: 152062 Hom.: 3309 Cov.: 33

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.197

GnomAD2 exomes AF: 0.230 AC: 56284 AN: 244492 AF XY: 0.238

Gnomad AFR exome AF: 0.120

Gnomad AMR exome AF: 0.209

Gnomad ASJ exome AF: 0.200

Gnomad EAS exome AF: 0.247

Gnomad FIN exome AF: 0.221

Gnomad NFE exome AF: 0.224

Gnomad OTH exome AF: 0.227

GnomAD4 exome AF: 0.229 AC: 333544 AN: 1458294 Hom.: 39293 Cov.: 34 AF XY: 0.232 AC XY: 168610 AN XY: 725288

African (AFR) AF: 0.116 AC: 3884 AN: 33396

American (AMR) AF: 0.210 AC: 9358 AN: 44474

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 5260 AN: 26074

East Asian (EAS) AF: 0.221 AC: 8778 AN: 39654

South Asian (SAS) AF: 0.337 AC: 28934 AN: 85792

European-Finnish (FIN) AF: 0.221 AC: 11793 AN: 53288

Middle Eastern (MID) AF: 0.217 AC: 943 AN: 4346

European-Non Finnish (NFE) AF: 0.226 AC: 250773 AN: 1111104

Other (OTH) AF: 0.230 AC: 13821 AN: 60166

GnomAD4 genome AF: 0.202 AC: 30808 AN: 152180 Hom.: 3312 Cov.: 33 AF XY: 0.206 AC XY: 15320 AN XY: 74394

African (AFR) AF: 0.123 AC: 5112 AN: 41534

American (AMR) AF: 0.236 AC: 3602 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 695 AN: 3470

East Asian (EAS) AF: 0.244 AC: 1264 AN: 5174

South Asian (SAS) AF: 0.358 AC: 1726 AN: 4824

European-Finnish (FIN) AF: 0.217 AC: 2304 AN: 10618

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15464 AN: 67960

Other (OTH) AF: 0.198 AC: 418 AN: 2106

Alfa AF: 0.205 Hom.: 1516

Bravo AF: 0.194

Asia WGS AF: 0.268 AC: 930 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

TREH-related disorder Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	1.5
DANN	Benign	0.88
PhyloP100		-1.0
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs7928371; hg19: chr11-118529127; COSMIC: COSV50622216; COSMIC: COSV50622216;