rs1867991

Variant names:

• chr10-116592393-A-C
• rs1867991
• NM_006229.4:c.205-23A>C

Your query was ambiguous. Multiple possible variants found:

• chr10-116592393-A-C
• chr10-116592393-A-G
• chr10-116592393-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006229.4(PNLIPRP1):​c.205-23A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 1,570,664 control chromosomes in the GnomAD database, including 389,833 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.67 (34843 hom., cov: 32)
  • Exomes 𝑓: 0.71 (354990 hom.)
• Consequence: PNLIPRP1 NM_006229.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 9 publications found

Genes affected

PNLIPRP1 (HGNC:9156): (pancreatic lipase related protein 1) Predicted to enable calcium ion binding activity. Predicted to be involved in lipid catabolic process. Predicted to be located in extracellular region. Biomarker of prostate cancer. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNLIPRP1	NM_006229.4	c.205-23A>C		intron_variant	Intron 3 of 12	ENST00000358834.9	NP_006220.1
PNLIPRP1	NM_001303135.1	c.205-23A>C		intron_variant	Intron 3 of 12		NP_001290064.1
PNLIPRP1	XM_047425364.1	c.205-23A>C		intron_variant	Intron 3 of 8		XP_047281320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNLIPRP1	ENST00000358834.9	c.205-23A>C		intron_variant	Intron 3 of 12	1	NM_006229.4	ENSP00000351695.4

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102489 AN: 151928 Hom.: 34817 Cov.: 32

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.683

GnomAD2 exomes AF: 0.697 AC: 158080 AN: 226742 AF XY: 0.699

Gnomad AFR exome AF: 0.602

Gnomad AMR exome AF: 0.739

Gnomad ASJ exome AF: 0.701

Gnomad EAS exome AF: 0.623

Gnomad FIN exome AF: 0.689

Gnomad NFE exome AF: 0.716

Gnomad OTH exome AF: 0.704

GnomAD4 exome AF: 0.706 AC: 1002231 AN: 1418618 Hom.: 354990 Cov.: 36 AF XY: 0.707 AC XY: 494669 AN XY: 700008

African (AFR) AF: 0.599 AC: 19172 AN: 32000

American (AMR) AF: 0.733 AC: 29134 AN: 39736

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 16675 AN: 23704

East Asian (EAS) AF: 0.625 AC: 24465 AN: 39128

South Asian (SAS) AF: 0.690 AC: 55122 AN: 79926

European-Finnish (FIN) AF: 0.696 AC: 36244 AN: 52076

Middle Eastern (MID) AF: 0.668 AC: 3658 AN: 5480

European-Non Finnish (NFE) AF: 0.714 AC: 776960 AN: 1088232

Other (OTH) AF: 0.699 AC: 40801 AN: 58336

GnomAD4 genome AF: 0.675 AC: 102567 AN: 152046 Hom.: 34843 Cov.: 32 AF XY: 0.675 AC XY: 50131 AN XY: 74314

African (AFR) AF: 0.601 AC: 24912 AN: 41462

American (AMR) AF: 0.688 AC: 10511 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 2473 AN: 3468

East Asian (EAS) AF: 0.616 AC: 3161 AN: 5128

South Asian (SAS) AF: 0.679 AC: 3271 AN: 4814

European-Finnish (FIN) AF: 0.690 AC: 7299 AN: 10574

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.716 AC: 48673 AN: 67994

Other (OTH) AF: 0.682 AC: 1442 AN: 2114

Alfa AF: 0.701 Hom.: 111468

Bravo AF: 0.671

Asia WGS AF: 0.621 AC: 2162 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	0.96
DANN	Benign	0.35
PhyloP100		-1.1
BranchPoint Hunter		2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1867991; hg19: chr10-118351905; COSMIC: COSV62610786; COSMIC: COSV62610786;