19-43578277-C-A

Position:

• chr19-43578277-C-A

Variant summary

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

The NM_001193621.3(PINLYP):​c.71-313C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,122 control chromosomes in the GnomAD database, including 2,074 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 0.16 (2074 hom., cov: 31)
• Consequence: PINLYP NM_001193621.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.73

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]

ENSG00000268361 (HGNC:):

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=-0.62).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PINLYP	NM_001193621.3	c.71-313C>A		intron_variant		ENST00000599207.6	NP_001180550.2
PINLYP	XM_047438830.1	c.143-313C>A		intron_variant			XP_047294786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PINLYP	ENST00000599207.6	c.71-313C>A		intron_variant		5	NM_001193621.3	ENSP00000469886.1
ENSG00000268361	ENST00000594374.1	c.168+14591G>T		intron_variant		3		ENSP00000472698.1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24535 AN: 152004 Hom.: 2076 Cov.: 31

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.161 AC: 24547 AN: 152122 Hom.: 2074 Cov.: 31 AF XY: 0.159 AC XY: 11820 AN XY: 74380

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.00173

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.155

Alfa AF: 0.181 Hom.: 3632

Bravo AF: 0.156

Asia WGS AF: 0.0600 AC: 212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	14
DANN	Benign	0.79

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: rs2682587; hg19: chr19-44082429;