rs745663

chr11-118658886-A-Gchr11-118658886-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. Variant has been reported in Lovd as Benign (no stars).

• 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

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-118658886-A-G is Benign according to our data. Variant chr11-118658886-A-G is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
TREH	NM_007180.3	c.1545+19T>C		intron_variant		ENST00000264029.9
TREH	NM_001301065.2	c.1452+19T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TREH	ENST00000264029.9	c.1545+19T>C		intron_variant		1	NM_007180.3	P1
TREH	ENST00000397925.2	c.1452+19T>C		intron_variant		1
TREH	ENST00000613915.4	c.*1322+19T>C		intron_variant, NMD_transcript_variant		2

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

GnomAD3 exomes AF: 0.347 AC: 86381 AN: 248982 Hom.: 16545 AF XY: 0.331 AC XY: 44755 AN XY: 135068

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 SAS exome AF: 0.196

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

Gnomad4 AFR exome AF: 0.236

Gnomad4 AMR exome AF: 0.539

Gnomad4 ASJ exome AF: 0.370

Gnomad4 EAS exome AF: 0.471

Gnomad4 SAS exome AF: 0.198

Gnomad4 FIN exome AF: 0.341

Gnomad4 NFE exome AF: 0.323

Gnomad4 OTH exome AF: 0.311

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

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.327

Alfa AF: 0.318 Hom.: 6837

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs745663; hg19: chr11-118529595; COSMIC: COSV50627829; COSMIC: COSV50627829;