19-43577347-A-G

Variant summary

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

The NM_001193621.3(PINLYP):c.70+86A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 1,315,628 control chromosomes in the GnomAD database, including 392,016 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 0.80 (49219 hom., cov: 28)
  • Exomes 𝑓: 0.77 (342797 hom.)
• Consequence: PINLYP NM_001193621.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PINLYP	NM_001193621.3	c.70+86A>G		intron_variant		ENST00000599207.6
PINLYP	XM_047438830.1	c.142+86A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PINLYP	ENST00000599207.6	c.70+86A>G		intron_variant		5	NM_001193621.3	P2

Frequencies

GnomAD3 genomes AF: 0.805 AC: 121982 AN: 151562 Hom.: 49193 Cov.: 28

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.814

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.811

GnomAD4 exome AF: 0.770 AC: 896566 AN: 1163954 Hom.: 342797 AF XY: 0.769 AC XY: 440005 AN XY: 571938

Gnomad4 AFR exome AF: 0.805

Gnomad4 AMR exome AF: 0.866

Gnomad4 ASJ exome AF: 0.797

Gnomad4 EAS exome AF: 0.871

Gnomad4 SAS exome AF: 0.760

Gnomad4 FIN exome AF: 0.717

Gnomad4 NFE exome AF: 0.765

Gnomad4 OTH exome AF: 0.782

GnomAD4 genome AF: 0.805 AC: 122063 AN: 151674 Hom.: 49219 Cov.: 28 AF XY: 0.805 AC XY: 59639 AN XY: 74100

Gnomad4 AFR AF: 0.827

Gnomad4 AMR AF: 0.870

Gnomad4 ASJ AF: 0.814

Gnomad4 EAS AF: 0.882

Gnomad4 SAS AF: 0.774

Gnomad4 FIN AF: 0.734

Gnomad4 NFE AF: 0.782

Gnomad4 OTH AF: 0.810

Alfa AF: 0.784 Hom.: 5498

Bravo AF: 0.821

Asia WGS AF: 0.804 AC: 2795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	7.8
Dann	Benign	0.61

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: rs2682586; hg19: chr19-44081499;