chr11-118658994-G-A

Position:

• chr11-118658994-G-A

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. 13/18 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.

• 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	Protein	UniProt
TREH	NM_007180.3	c.1456C>T	p.Arg486Trp	missense_variant	13/15	ENST00000264029.9	NP_009111.2
TREH	NM_001301065.2	c.1363C>T	p.Arg455Trp	missense_variant	12/14		NP_001287994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TREH	ENST00000264029.9	c.1456C>T	p.Arg486Trp	missense_variant	13/15	1	NM_007180.3	ENSP00000264029	P1
TREH	ENST00000397925.2	c.1363C>T	p.Arg455Trp	missense_variant	12/14	1		ENSP00000381020
TREH	ENST00000613915.4	c.*1233C>T		3_prime_UTR_variant, NMD_transcript_variant	11/13	2		ENSP00000477923

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;