NM_007180.3:c.-265A>C

Variant names:

• chr11-118679892-T-G
• rs673770
• NM_007180.3:c.-265A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007180.3(TREH):​c.-265A>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 151,080 control chromosomes in the GnomAD database, including 9,340 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 0.35 (9340 hom., cov: 30)
• Consequence: TREH NM_007180.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.352
• Publications: 13 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TREH	NM_007180.3	c.-265A>C		upstream_gene_variant		ENST00000264029.9	NP_009111.2
TREH	NM_001301065.2	c.-265A>C		upstream_gene_variant			NP_001287994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TREH	ENST00000264029.9	c.-265A>C		upstream_gene_variant		1	NM_007180.3	ENSP00000264029.5

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52214 AN: 150962 Hom.: 9318 Cov.: 30

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.353

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.353

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.346 AC: 52281 AN: 151080 Hom.: 9340 Cov.: 30 AF XY: 0.345 AC XY: 25409 AN XY: 73752

African (AFR) AF: 0.341 AC: 14010 AN: 41126

American (AMR) AF: 0.472 AC: 7155 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1270 AN: 3466

East Asian (EAS) AF: 0.441 AC: 2260 AN: 5124

South Asian (SAS) AF: 0.197 AC: 944 AN: 4790

European-Finnish (FIN) AF: 0.309 AC: 3220 AN: 10404

Middle Eastern (MID) AF: 0.366 AC: 106 AN: 290

European-Non Finnish (NFE) AF: 0.327 AC: 22143 AN: 67718

Other (OTH) AF: 0.352 AC: 739 AN: 2100

Alfa AF: 0.331 Hom.: 20889

Bravo AF: 0.366

Asia WGS AF: 0.304 AC: 1059 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.0
DANN	Benign	0.58
PhyloP100		0.35
PromoterAI		0.021	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs673770; hg19: chr11-118550601;