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. The variant received -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
• Publications: 52 publications found

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]

LOC124903758 (HGNC:):

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]

ACMG classification

Our verdict: Benign. The variant received -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
LOC124903758	XR_007065185.1	n.-90G>A		upstream_gene_variant
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

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

African (AFR) AF: 0.108 AC: 4481 AN: 41480

American (AMR) AF: 0.369 AC: 5624 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1904 AN: 3468

East Asian (EAS) AF: 0.0197 AC: 102 AN: 5178

South Asian (SAS) AF: 0.237 AC: 1139 AN: 4814

European-Finnish (FIN) AF: 0.386 AC: 4064 AN: 10522

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30821 AN: 67962

Other (OTH) AF: 0.413 AC: 869 AN: 2106

Alfa AF: 0.403 Hom.: 37771

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
PhyloP100		0.053

Splicing

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

Other links and lift over

dbSNP: rs154657; hg19: chr16-89708096;