dbSNP rs3810378: PINLYP:c.70+188G>C (chr19-43577449-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001193621.3(PINLYP):c.70+188G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 151,960 control chromosomes in the GnomAD database, including 6,817 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 0.29 ( 6817 hom., cov: 30)

Consequence

PINLYP
NM_001193621.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.02

Publications

16 publications found

Variant links:

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]

PINLYP links:

ENSG00000268361 (HGNC:):

ENSG00000268361 links:

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)

XRCC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PINLYP	NM_001193621.3 link	c.70+188G>C		intron_variant	Intron 2 of 5	ENST00000599207.6	NP_001180550.2	A6NC86-1
PINLYP	XM_047438830.1 link	c.142+188G>C		intron_variant	Intron 1 of 4		XP_047294786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PINLYP	ENST00000599207.6 link	c.70+188G>C		intron_variant	Intron 2 of 5	5	NM_001193621.3	ENSP00000469886.1		A6NC86-1
ENSG00000268361	ENST00000594374.1 link	c.168+15419C>G		intron_variant	Intron 1 of 2	3		ENSP00000472698.1		M0R2N6

Frequencies

GnomAD3 genomes

AF:

0.288

AC:

43792

AN:

151842

Hom.:

6809

Cov.:

show subpopulations

Gnomad AFR

AF:

0.153

Gnomad AMI

AF:

0.433

Gnomad AMR

AF:

0.304

Gnomad ASJ

AF:

0.388

Gnomad EAS

AF:

0.271

Gnomad SAS

AF:

0.346

Gnomad FIN

AF:

0.310

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.354

Gnomad OTH

AF:

0.282

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

GnomAD4 genome

AF:

0.288

AC:

43806

AN:

151960

Hom.:

6817

Cov.:

AF XY:

0.286

AC XY:

21224

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.153

AC:

6360

AN:

41464

American (AMR)

AF:

0.304

AC:

4640

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.388

AC:

1346

AN:

3472

East Asian (EAS)

AF:

0.270

AC:

1396

AN:

5162

South Asian (SAS)

AF:

0.346

AC:

1663

AN:

4808

European-Finnish (FIN)

AF:

0.310

AC:

3268

AN:

10548

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.354

AC:

24064

AN:

67930

Other (OTH)

AF:

0.285

AC:

601

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1510

3020

4529

6039

7549

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

454

908

1362

1816

2270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.312

Hom.:

1002

Bravo

AF:

0.280

Asia WGS

AF:

0.292

AC:

1015

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.36

(source)

DANN

Benign

0.33

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over