rs2276064

Variant names:

• chr11-118658994-G-A
• rs2276064
• NM_007180.3:c.1456C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-118658994-G-A
• chr11-118658994-G-C
• chr11-118658994-G-T

Variant summary

Our verdict is Benign. The variant received -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. 14/19 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R486Q) has been classified as Uncertain significance.

• 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
• Publications: 21 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 (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 rank	MANE	Protein	UniProt
TREH	NM_007180.3	c.1456C>T	p.Arg486Trp	missense_variant	Exon 13 of 15	ENST00000264029.9	NP_009111.2
TREH	NM_001301065.2	c.1363C>T	p.Arg455Trp	missense_variant	Exon 12 of 14		NP_001287994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TREH	ENST00000264029.9	c.1456C>T	p.Arg486Trp	missense_variant	Exon 13 of 15	1	NM_007180.3	ENSP00000264029.5
TREH	ENST00000397925.2	c.1363C>T	p.Arg455Trp	missense_variant	Exon 12 of 14	1		ENSP00000381020.2
TREH	ENST00000613915.4	n.*1233C>T		non_coding_transcript_exon_variant	Exon 11 of 13	2		ENSP00000477923.1
TREH	ENST00000613915.4	n.*1233C>T		3_prime_UTR_variant	Exon 11 of 13	2		ENSP00000477923.1

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

GnomAD2 exomes AF: 0.0860 AC: 21421 AN: 249154 AF XY: 0.0743

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 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

African (AFR) AF: 0.00376 AC: 126 AN: 33480

American (AMR) AF: 0.262 AC: 11718 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0759 AC: 1984 AN: 26126

East Asian (EAS) AF: 0.470 AC: 18651 AN: 39700

South Asian (SAS) AF: 0.0414 AC: 3568 AN: 86254

European-Finnish (FIN) AF: 0.00708 AC: 377 AN: 53270

Middle Eastern (MID) AF: 0.0182 AC: 105 AN: 5766

European-Non Finnish (NFE) AF: 0.0129 AC: 14393 AN: 1111816

Other (OTH) AF: 0.0413 AC: 2491 AN: 60366

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

African (AFR) AF: 0.00635 AC: 264 AN: 41548

American (AMR) AF: 0.126 AC: 1926 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0767 AC: 266 AN: 3468

East Asian (EAS) AF: 0.415 AC: 2136 AN: 5152

South Asian (SAS) AF: 0.0502 AC: 242 AN: 4822

European-Finnish (FIN) AF: 0.00527 AC: 56 AN: 10622

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0139 AC: 945 AN: 68030

Other (OTH) AF: 0.0435 AC: 92 AN: 2114

Alfa AF: 0.0344 Hom.: 1379

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
PhyloP100		0.033
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
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

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