chr16-89614460-C-T

Position:

• chr16-89614460-C-T

Variant summary

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

The NM_001389466.1(DPEP1):​c.-107+741C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,148 control chromosomes in the GnomAD database, including 4,105 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 0.23 (4105 hom., cov: 32)
• Consequence: DPEP1 NM_001389466.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

Genes affected

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPEP1	NM_001389466.1	c.-107+741C>T		intron_variant		ENST00000690203.1	NP_001376395.1
DPEP1	NM_001128141.3	c.-107+1056C>T		intron_variant			NP_001121613.1
DPEP1	NM_001389470.1	c.-107+741C>T		intron_variant			NP_001376399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPEP1	ENST00000690203.1	c.-107+741C>T		intron_variant			NM_001389466.1	ENSP00000508584	P1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34574 AN: 152030 Hom.: 4099 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.0331

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.227 AC: 34587 AN: 152148 Hom.: 4105 Cov.: 32 AF XY: 0.223 AC XY: 16612 AN XY: 74392

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.0331

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.238

Alfa AF: 0.233 Hom.: 5198

Bravo AF: 0.227

Asia WGS AF: 0.179 AC: 623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs16965867; hg19: chr16-89680868;