ENST00000676275.1:n.524-213C>T

Variant names:

• chr16-89641688-G-A
• rs154657
• ENST00000676275.1:n.524-213C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000676275.1(CHMP1A):​n.524-213C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 151,992 control chromosomes in the GnomAD database, including 10,272 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 0.33 (10272 hom., cov: 32)
• Consequence: CHMP1A ENST00000676275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530

Genes affected

CHMP1A (HGNC:8740): (charged multivesicular body protein 1A) This gene encodes a member of the CHMP/Chmp family of proteins which are involved in multivesicular body sorting of proteins to the interiors of lysosomes. The initial prediction of the protein sequence encoded by this gene suggested that the encoded protein was a metallopeptidase. The nomenclature has been updated recently to reflect the correct biological function of this encoded protein. Several transcripts encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

DPEP1 (HGNC:3002): (dipeptidase 1) The protein encoded by this gene is a kidney membrane enzyme involved in the metabolism of glutathione and other similar proteins by dipeptide hydrolysis. The encoded protein is known to regulate leukotriene activity by catalyzing the conversion of leukotriene D4 to leukotriene E4. This protein uses zinc as a cofactor and acts as a disulfide-linked homodimer. [provided by RefSeq, Dec 2020]

LOC124903758 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPEP1	NM_001389470.1	c.*1083G>A		downstream_gene_variant			NP_001376399.1
DPEP1	NM_001389471.1	c.*1083G>A		downstream_gene_variant			NP_001376400.1
DPEP1	XM_047433691.1	c.*1083G>A		downstream_gene_variant			XP_047289647.1
LOC124903758	XR_007065185.1	n.-90G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHMP1A	ENST00000676275.1	n.524-213C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49744 AN: 151874 Hom.: 10271 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.0198

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.327 AC: 49736 AN: 151992 Hom.: 10272 Cov.: 32 AF XY: 0.322 AC XY: 23919 AN XY: 74254

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.549

Gnomad4 EAS AF: 0.0197

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.413

Alfa AF: 0.442 Hom.: 15225

Bravo AF: 0.318

Asia WGS AF: 0.140 AC: 487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	10
DANN	Benign	0.92

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs154657; hg19: chr16-89708096;