chr11-82938726-G-T

Variant names:

• chr11-82938726-G-T
• rs10792665
• ENST00000525361.5:c.511+6877G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDIAS	ENST00000525361.5	c.511+6877G>T		intron_variant	Intron 7 of 7	2		ENSP00000435424.1
PRCP	ENST00000534396.5	c.-148+18339C>A		intron_variant	Intron 2 of 5	5		ENSP00000432506.1

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

African (AFR) AF: 0.362 AC: 14974 AN: 41344

American (AMR) AF: 0.504 AC: 7689 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1692 AN: 3468

East Asian (EAS) AF: 0.340 AC: 1755 AN: 5160

South Asian (SAS) AF: 0.388 AC: 1860 AN: 4796

European-Finnish (FIN) AF: 0.454 AC: 4760 AN: 10488

Middle Eastern (MID) AF: 0.473 AC: 138 AN: 292

European-Non Finnish (NFE) AF: 0.442 AC: 29998 AN: 67932

Other (OTH) AF: 0.449 AC: 945 AN: 2104

Alfa AF: 0.447 Hom.: 8177

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
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10792665; hg19: chr11-82649768;