rs17655484

Variant names:

• chr19-43580199-G-T
• rs17655484
• NM_001193621.3:c.188-1013G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.15 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.188-1013G>T		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.188-1013G>T		intron	N/A	ENSP00000469886.1	A6NC86-1
	ENSG00000268361	ENST00000594374.1	TSL:3	c.168+12669C>A		intron	N/A	ENSP00000472698.1	M0R2N6
	XRCC1	ENST00000598165.5	TSL:3	c.72+166C>A		intron	N/A	ENSP00000470045.1	M0QYS5

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

African (AFR) AF: 0.115 AC: 4759 AN: 41484

American (AMR) AF: 0.155 AC: 2362 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0878 AC: 304 AN: 3464

East Asian (EAS) AF: 0.105 AC: 544 AN: 5166

South Asian (SAS) AF: 0.0458 AC: 220 AN: 4804

European-Finnish (FIN) AF: 0.110 AC: 1167 AN: 10592

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0861 AC: 5853 AN: 67990

Other (OTH) AF: 0.0971 AC: 205 AN: 2112

Alfa AF: 0.0960 Hom.: 96

Bravo AF: 0.108

Asia WGS AF: 0.0890 AC: 307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.0
DANN	Benign	0.69
PhyloP100		1.0
PromoterAI		0.020	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17655484; hg19: chr19-44084351;