16-89614460-C-T

Variant names:

• chr16-89614460-C-T
• rs16965867
• NM_001389466.1:c.-107+741C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001389466.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPEP1	NM_001389466.1	MANE Select	c.-107+741C>T		intron	N/A	NP_001376395.1
	DPEP1	NM_001128141.3		c.-107+1056C>T		intron	N/A	NP_001121613.1
	DPEP1	NM_001389470.1		c.-107+741C>T		intron	N/A	NP_001376399.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPEP1	ENST00000690203.1	MANE Select	c.-107+741C>T		intron	N/A	ENSP00000508584.1
	DPEP1	ENST00000421184.5	TSL:5	c.-107+1056C>T		intron	N/A	ENSP00000397313.1
	DPEP1	ENST00000570029.5	TSL:3	c.-107+1056C>T		intron	N/A	ENSP00000455916.1

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

African (AFR) AF: 0.251 AC: 10426 AN: 41500

American (AMR) AF: 0.212 AC: 3240 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 991 AN: 3470

East Asian (EAS) AF: 0.0331 AC: 172 AN: 5190

South Asian (SAS) AF: 0.350 AC: 1685 AN: 4818

European-Finnish (FIN) AF: 0.153 AC: 1621 AN: 10612

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15721 AN: 67956

Other (OTH) AF: 0.238 AC: 504 AN: 2116

Alfa AF: 0.231 Hom.: 13429

Bravo AF: 0.227

Asia WGS AF: 0.179 AC: 623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.59
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16965867; hg19: chr16-89680868;