rs3810378

Positions:

• chr19-43577449-G-C

Variant summary

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

The NM_001193621.3(PINLYP):​c.70+188G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 151,960 control chromosomes in the GnomAD database, including 6,817 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 0.29 (6817 hom., cov: 30)
• Consequence: PINLYP NM_001193621.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

Genes affected

PINLYP (HGNC:44206): (phospholipase A2 inhibitor and LY6/PLAUR domain containing) Predicted to enable phospholipase inhibitor activity. Predicted to be involved in negative regulation of catalytic activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

XRCC1 (HGNC:12828): (X-ray repair cross complementing 1) The protein encoded by this gene is involved in the efficient repair of DNA single-strand breaks formed by exposure to ionizing radiation and alkylating agents. This protein interacts with DNA ligase III, polymerase beta and poly (ADP-ribose) polymerase to participate in the base excision repair pathway. It may play a role in DNA processing during meiogenesis and recombination in germ cells. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PINLYP	NM_001193621.3	c.70+188G>C		intron_variant		ENST00000599207.6	NP_001180550.2
PINLYP	XM_047438830.1	c.142+188G>C		intron_variant			XP_047294786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PINLYP	ENST00000599207.6	c.70+188G>C		intron_variant		5	NM_001193621.3	ENSP00000469886	P2

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43792 AN: 151842 Hom.: 6809 Cov.: 30

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.288 AC: 43806 AN: 151960 Hom.: 6817 Cov.: 30 AF XY: 0.286 AC XY: 21224 AN XY: 74250

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.285

Alfa AF: 0.312 Hom.: 1002

Bravo AF: 0.280

Asia WGS AF: 0.292 AC: 1015 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.36
DANN	Benign	0.33

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: rs3810378; hg19: chr19-44081601; COSMIC: COSV53451531; COSMIC: COSV53451531;