19-43577347-A-G

Variant names:

• chr19-43577347-A-G
• rs2682586
• NM_001193621.3:c.70+86A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.861 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PINLYP	NM_001193621.3	MANE Select	c.70+86A>G		intron	N/A	NP_001180550.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PINLYP	ENST00000599207.6	TSL:5 MANE Select	c.70+86A>G		intron	N/A	ENSP00000469886.1
	ENSG00000268361	ENST00000594374.1	TSL:3	c.168+15521T>C		intron	N/A	ENSP00000472698.1
	XRCC1	ENST00000598165.5	TSL:3	c.73-2345T>C		intron	N/A	ENSP00000470045.1

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

African (AFR) AF: 0.805 AC: 20383 AN: 25316

American (AMR) AF: 0.866 AC: 17662 AN: 20392

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 14722 AN: 18464

East Asian (EAS) AF: 0.871 AC: 27562 AN: 31658

South Asian (SAS) AF: 0.760 AC: 43447 AN: 57180

European-Finnish (FIN) AF: 0.717 AC: 19529 AN: 27228

Middle Eastern (MID) AF: 0.838 AC: 4091 AN: 4880

European-Non Finnish (NFE) AF: 0.765 AC: 711504 AN: 930644

Other (OTH) AF: 0.782 AC: 37666 AN: 48192

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

African (AFR) AF: 0.827 AC: 34210 AN: 41374

American (AMR) AF: 0.870 AC: 13250 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.814 AC: 2820 AN: 3464

East Asian (EAS) AF: 0.882 AC: 4539 AN: 5144

South Asian (SAS) AF: 0.774 AC: 3711 AN: 4792

European-Finnish (FIN) AF: 0.734 AC: 7711 AN: 10500

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.782 AC: 53098 AN: 67864

Other (OTH) AF: 0.810 AC: 1710 AN: 2110

Alfa AF: 0.786 Hom.: 5764

Bravo AF: 0.821

Asia WGS AF: 0.804 AC: 2795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	7.8
DANN	Benign	0.61
PhyloP100		1.5
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: rs2682586; hg19: chr19-44081499;