rs2276064

chr11-118658994-G-Achr11-118658994-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007180.3(TREH):c.1456C>T(p.Arg486Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0368 in 1,613,748 control chromosomes in the GnomAD database, including 7,497 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R486Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.039 (681 hom., cov: 33)
  • Exomes 𝑓: 0.037 (6816 hom.)
• Consequence: TREH NM_007180.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00507015).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TREH	NM_007180.3	c.1456C>T	p.Arg486Trp	missense_variant	13/15	ENST00000264029.9
TREH	NM_001301065.2	c.1363C>T	p.Arg455Trp	missense_variant	12/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TREH	ENST00000264029.9	c.1456C>T	p.Arg486Trp	missense_variant	13/15	1	NM_007180.3	P1
TREH	ENST00000397925.2	c.1363C>T	p.Arg455Trp	missense_variant	12/14	1
TREH	ENST00000613915.4	c.*1233C>T		3_prime_UTR_variant, NMD_transcript_variant	11/13	2

Frequencies

GnomAD3 genomes AF: 0.0390 AC: 5932 AN: 152138 Hom.: 679 Cov.: 33

Gnomad AFR AF: 0.00637

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0767

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.0506

Gnomad FIN AF: 0.00527

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0139

Gnomad OTH AF: 0.0421

GnomAD3 exomes AF: 0.0860 AC: 21421 AN: 249154 Hom.: 3311 AF XY: 0.0743 AC XY: 10043 AN XY: 135196

Gnomad AFR exome AF: 0.00478

Gnomad AMR exome AF: 0.282

Gnomad ASJ exome AF: 0.0762

Gnomad EAS exome AF: 0.409

Gnomad SAS exome AF: 0.0429

Gnomad FIN exome AF: 0.00594

Gnomad NFE exome AF: 0.0151

Gnomad OTH exome AF: 0.0572

GnomAD4 exome AF: 0.0365 AC: 53413 AN: 1461492 Hom.: 6816 Cov.: 34 AF XY: 0.0356 AC XY: 25887 AN XY: 727064

Gnomad4 AFR exome AF: 0.00376

Gnomad4 AMR exome AF: 0.262

Gnomad4 ASJ exome AF: 0.0759

Gnomad4 EAS exome AF: 0.470

Gnomad4 SAS exome AF: 0.0414

Gnomad4 FIN exome AF: 0.00708

Gnomad4 NFE exome AF: 0.0129

Gnomad4 OTH exome AF: 0.0413

GnomAD4 genome AF: 0.0390 AC: 5934 AN: 152256 Hom.: 681 Cov.: 33 AF XY: 0.0419 AC XY: 3117 AN XY: 74444

Gnomad4 AFR AF: 0.00635

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.0767

Gnomad4 EAS AF: 0.415

Gnomad4 SAS AF: 0.0502

Gnomad4 FIN AF: 0.00527

Gnomad4 NFE AF: 0.0139

Gnomad4 OTH AF: 0.0435

Alfa AF: 0.0362 Hom.: 1197

Bravo AF: 0.0536

TwinsUK AF: 0.0102 AC: 38

ALSPAC AF: 0.0127 AC: 49

ESP6500AA AF: 0.00551 AC: 22

ESP6500EA AF: 0.0183 AC: 152

ExAC AF: 0.0763 AC: 9225

Asia WGS AF: 0.191 AC: 664 AN: 3478

EpiCase AF: 0.0162

EpiControl AF: 0.0142

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	17
Dann	Benign	0.97
DEOGEN2	Benign	0.049	T;.
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.61	T;T
MetaRNN	Benign	0.0051	T;T
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	1.0	P;P;P;P;P;P
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.37	N;N
REVEL	Benign	0.031
Sift	Benign	0.16	T;T
Sift4G	Benign	0.15	T;T
Polyphen		0.076	B;.
Vest4		0.068
MPC		0.032
ClinPred		0.0059	T
GERP RS		2.4
Varity_R		0.076
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2276064; hg19: chr11-118529703; COSMIC: COSV50619475; COSMIC: COSV50619475;