10-116562757-A-G

Position:

• chr10-116562757-A-G

Variant summary

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

The NM_000936.4(PNLIP):​c.1334+1121A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.886 in 152,210 control chromosomes in the GnomAD database, including 59,993 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 0.89 (59993 hom., cov: 32)
• Consequence: PNLIP NM_000936.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.929

Genes affected

PNLIP (HGNC:9155): (pancreatic lipase) This gene encodes a member of the lipase family of proteins. The encoded enzyme is secreted by the pancreas and hydrolyzes triglycerides in the small intestine, and is essential for the efficient digestion of dietary fats. Inhibition of the encoded enzyme may prevent high-fat diet-induced obesity in mice and result in weight loss in human patients with obesity. Mutations in this gene cause congenital pancreatic lipase deficiency, a rare disorder characterized by steatorrhea. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNLIP	NM_000936.4	c.1334+1121A>G		intron_variant		ENST00000369221.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNLIP	ENST00000369221.2	c.1334+1121A>G		intron_variant		1	NM_000936.4	P1

Frequencies

GnomAD3 genomes AF: 0.886 AC: 134746 AN: 152092 Hom.: 59950 Cov.: 32

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.882

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.919

Gnomad FIN AF: 0.913

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.919

Gnomad OTH AF: 0.904

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

GnomAD4 genome AF: 0.886 AC: 134843 AN: 152210 Hom.: 59993 Cov.: 32 AF XY: 0.884 AC XY: 65771 AN XY: 74396

Gnomad4 AFR AF: 0.857

Gnomad4 AMR AF: 0.863

Gnomad4 ASJ AF: 0.882

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.919

Gnomad4 FIN AF: 0.913

Gnomad4 NFE AF: 0.919

Gnomad4 OTH AF: 0.900

Alfa AF: 0.913 Hom.: 58999

Bravo AF: 0.878

Asia WGS AF: 0.815 AC: 2834 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	0.12
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2915772; hg19: chr10-118322269;