rs17655484

Positions:

• chr19-43580199-G-T

Variant summary

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

The NM_001193621.3(PINLYP):​c.188-1013G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,082 control chromosomes in the GnomAD database, including 931 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 0.10 (931 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]

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PINLYP	NM_001193621.3	c.188-1013G>T		intron_variant		ENST00000599207.6	NP_001180550.2
PINLYP	XM_011526971.3	c.-183G>T		5_prime_UTR_variant	1/4		XP_011525273.1
PINLYP	XM_047438830.1	c.260-1013G>T		intron_variant			XP_047294786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PINLYP	ENST00000599207.6	c.188-1013G>T		intron_variant		5	NM_001193621.3	ENSP00000469886.1
ENSG00000268361	ENST00000594374.1	c.168+12669C>A		intron_variant		3		ENSP00000472698.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15445 AN: 151964 Hom.: 927 Cov.: 30

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.0878

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0462

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0861

Gnomad OTH AF: 0.0981

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

GnomAD4 genome AF: 0.102 AC: 15448 AN: 152082 Hom.: 931 Cov.: 30 AF XY: 0.103 AC XY: 7647 AN XY: 74330

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.0878

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.0458

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.0861

Gnomad4 OTH AF: 0.0971

Alfa AF: 0.0959 Hom.: 93

Bravo AF: 0.108

Asia WGS AF: 0.0890 AC: 307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.0
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs17655484; hg19: chr19-44084351;