chr11-118659457-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_007180.3(TREH):c.1345T>C(p.Tyr449His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,604,718 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 19 hom., cov: 33)

Exomes 𝑓: 0.00098 ( 14 hom. )

Consequence

TREH
NM_007180.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.138

Publications

4 publications found

Variant links:

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

TREH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042777956).

BP6

Variant 11-118659457-A-G is Benign according to our data. Variant chr11-118659457-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 376781.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00999 (1521/152248) while in subpopulation AFR AF = 0.0345 (1431/41536). AF 95% confidence interval is 0.033. There are 19 homozygotes in GnomAd4. There are 693 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1521 AD gene.

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.1345T>C	p.Tyr449His	missense	Exon 12 of 15	NP_009111.2	O43280-1
	TREH	NM_001301065.2		c.1252T>C	p.Tyr418His	missense	Exon 11 of 14	NP_001287994.1	O43280-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TREH	ENST00000264029.9	TSL:1 MANE Select	c.1345T>C	p.Tyr449His	missense	Exon 12 of 15	ENSP00000264029.5	O43280-1
TREH	ENST00000397925.2	TSL:1	c.1252T>C	p.Tyr418His	missense	Exon 11 of 14	ENSP00000381020.2	O43280-2
TREH	ENST00000854539.1		c.1192T>C	p.Tyr398His	missense	Exon 11 of 14	ENSP00000524598.1

Frequencies

GnomAD3 genomes

AF:

0.00998

AC:

1519

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0345

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00491

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00253

AC:

596

AN:

236032

AF XY:

0.00182

show subpopulations

Gnomad AFR exome

AF:

0.0361

Gnomad AMR exome

AF:

0.00176

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000655

Gnomad OTH exome

AF:

0.000347

GnomAD4 exome

AF:

0.000980

AC:

1423

AN:

1452470

Hom.:

Cov.:

AF XY:

0.000846

AC XY:

610

AN XY:

721428

show subpopulations

African (AFR)

AF:

0.0347

AC:

1154

AN:

33244

American (AMR)

AF:

0.00172

AC:

AN:

43668

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25682

East Asian (EAS)

AF:

0.00

AC:

AN:

39502

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84574

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52904

Middle Eastern (MID)

AF:

0.00105

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.0000524

AC:

AN:

1107222

Other (OTH)

AF:

0.00215

AC:

129

AN:

59936

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

137

206

274

343

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00999

AC:

1521

AN:

152248

Hom.:

Cov.:

AF XY:

0.00931

AC XY:

693

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.0345

AC:

1431

AN:

41536

American (AMR)

AF:

0.00497

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

67994

Other (OTH)

AF:

0.00473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

158

236

315

394

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00396

Hom.:

Bravo

AF:

0.0111

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0338

AC:

130

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00289

AC:

349

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.72

CADD

Benign

8.1

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.076

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0011

LIST_S2

Benign

0.66

MetaRNN

Benign

0.0043

MetaSVM

Benign

-0.98

PhyloP100

-0.14

PrimateAI

Benign

0.32

PROVEAN

Benign

0.34

REVEL

Benign

0.057

Sift

Benign

0.083

Sift4G

Benign

0.075

Polyphen

0.0010

Vest4

0.11

MVP

0.11

MPC

0.037

ClinPred

0.0033

GERP RS

-9.0

Varity_R

0.047

gMVP

0.67

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over