rs745663

Variant names:

• chr11-118658886-A-G
• rs745663
• NM_007180.3:c.1545+19T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-118658886-A-G
• chr11-118658886-A-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.1545+19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 1,612,934 control chromosomes in the GnomAD database, including 88,396 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (7903 hom., cov: 33)
  • Exomes 𝑓: 0.33 (80493 hom.)
• Consequence: TREH NM_007180.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.857
• Publications: 15 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 (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TREH	NM_007180.3	c.1545+19T>C		intron_variant	Intron 13 of 14	ENST00000264029.9	NP_009111.2
TREH	NM_001301065.2	c.1452+19T>C		intron_variant	Intron 12 of 13		NP_001287994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TREH	ENST00000264029.9	c.1545+19T>C		intron_variant	Intron 13 of 14	1	NM_007180.3	ENSP00000264029.5
TREH	ENST00000397925.2	c.1452+19T>C		intron_variant	Intron 12 of 13	1		ENSP00000381020.2
TREH	ENST00000613915.4	n.*1322+19T>C		intron_variant	Intron 11 of 12	2		ENSP00000477923.1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47920 AN: 151996 Hom.: 7891 Cov.: 33

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.328

GnomAD2 exomes AF: 0.347 AC: 86381 AN: 248982 AF XY: 0.331

Gnomad AFR exome AF: 0.235

Gnomad AMR exome AF: 0.553

Gnomad ASJ exome AF: 0.371

Gnomad EAS exome AF: 0.410

Gnomad FIN exome AF: 0.341

Gnomad NFE exome AF: 0.330

Gnomad OTH exome AF: 0.339

GnomAD4 exome AF: 0.326 AC: 475566 AN: 1460820 Hom.: 80493 Cov.: 34 AF XY: 0.320 AC XY: 232864 AN XY: 726730

African (AFR) AF: 0.236 AC: 7893 AN: 33454

American (AMR) AF: 0.539 AC: 24097 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 9663 AN: 26100

East Asian (EAS) AF: 0.471 AC: 18679 AN: 39690

South Asian (SAS) AF: 0.198 AC: 17035 AN: 86234

European-Finnish (FIN) AF: 0.341 AC: 18217 AN: 53352

Middle Eastern (MID) AF: 0.332 AC: 1915 AN: 5766

European-Non Finnish (NFE) AF: 0.323 AC: 359324 AN: 1111170

Other (OTH) AF: 0.311 AC: 18743 AN: 60348

GnomAD4 genome AF: 0.315 AC: 47951 AN: 152114 Hom.: 7903 Cov.: 33 AF XY: 0.315 AC XY: 23454 AN XY: 74356

African (AFR) AF: 0.240 AC: 9971 AN: 41492

American (AMR) AF: 0.427 AC: 6531 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1292 AN: 3470

East Asian (EAS) AF: 0.418 AC: 2162 AN: 5176

South Asian (SAS) AF: 0.186 AC: 897 AN: 4824

European-Finnish (FIN) AF: 0.333 AC: 3526 AN: 10578

Middle Eastern (MID) AF: 0.360 AC: 105 AN: 292

European-Non Finnish (NFE) AF: 0.329 AC: 22335 AN: 67958

Other (OTH) AF: 0.327 AC: 691 AN: 2114

Alfa AF: 0.320 Hom.: 9444

Bravo AF: 0.326

Asia WGS AF: 0.274 AC: 956 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.17
DANN	Benign	0.39
PhyloP100		-0.86
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs745663; hg19: chr11-118529595; COSMIC: COSV50627829; COSMIC: COSV50627829;