rs10792665

Positions:

• chr11-82938726-G-T

Variant summary

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

The ENST00000525361.5(DDIAS):​c.511+6877G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 151,748 control chromosomes in the GnomAD database, including 13,812 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 0.42 (13812 hom., cov: 31)
• Consequence: DDIAS ENST00000525361.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.691

Genes affected

DDIAS (HGNC:26351): (DNA damage induced apoptosis suppressor) Involved in negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage and regulation of DNA stability. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PRCP (HGNC:9344): (prolylcarboxypeptidase) This gene encodes a member of the peptidase S28 family of serine exopeptidases. The encoded preproprotein is proteolytically processed to generate the mature lysosomal prolylcarboxypeptidase. This enzyme cleaves C-terminal amino acids linked to proline in peptides such as angiotension II, III and des-Arg9-bradykinin. The cleavage occurs at acidic pH, but the enzyme activity is retained with some substrates at neutral pH. This enzyme has been shown to be an activator of the cell matrix-associated prekallikrein. The importance of angiotension II, one of the substrates of this enzyme, in regulating blood pressure and electrolyte balance suggests that this gene may be related to essential hypertension. A pseudogene of this gene has been identified on chromosome 2. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDIAS	ENST00000525361.5	c.511+6877G>T		intron_variant		2		A2
PRCP	ENST00000534396.5	c.-148+18339C>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64119 AN: 151630 Hom.: 13797 Cov.: 31

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.423 AC: 64170 AN: 151748 Hom.: 13812 Cov.: 31 AF XY: 0.423 AC XY: 31349 AN XY: 74130

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.442

Gnomad4 OTH AF: 0.449

Alfa AF: 0.451 Hom.: 4719

Bravo AF: 0.427

Asia WGS AF: 0.386 AC: 1341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.74
DANN	Benign	0.31

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10792665; hg19: chr11-82649768;