rs2682587

Variant names:

• chr19-43578277-C-A
• rs2682587
• NM_001193621.3:c.71-313C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 25 publications found

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]

XRCC1 Gene-Disease associations (from GenCC):

• head and neck cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• spinocerebellar ataxia, autosomal recessive 26

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001193621.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PINLYP	NM_001193621.3	MANE Select	c.71-313C>A		intron	N/A	NP_001180550.2	A6NC86-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PINLYP	ENST00000599207.6	TSL:5 MANE Select	c.71-313C>A		intron	N/A	ENSP00000469886.1	A6NC86-1
	ENSG00000268361	ENST00000594374.1	TSL:3	c.168+14591G>T		intron	N/A	ENSP00000472698.1	M0R2N6
	XRCC1	ENST00000598165.5	TSL:3	c.72+2088G>T		intron	N/A	ENSP00000470045.1	M0QYS5

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

African (AFR) AF: 0.146 AC: 6046 AN: 41484

American (AMR) AF: 0.130 AC: 1992 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 477 AN: 3472

East Asian (EAS) AF: 0.00173 AC: 9 AN: 5190

South Asian (SAS) AF: 0.131 AC: 631 AN: 4826

European-Finnish (FIN) AF: 0.176 AC: 1861 AN: 10592

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12944 AN: 67972

Other (OTH) AF: 0.155 AC: 327 AN: 2110

Alfa AF: 0.180 Hom.: 5047

Bravo AF: 0.156

Asia WGS AF: 0.0600 AC: 212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	14
DANN	Benign	0.79
PhyloP100		2.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2682587; hg19: chr19-44082429;