17-2670358-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000430.4(PAFAH1B1):c.568+27C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.92 in 1,587,934 control chromosomes in the GnomAD database, including 672,222 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.89 ( 61041 hom., cov: 31)

Exomes 𝑓: 0.92 ( 611181 hom. )

Consequence

PAFAH1B1
NM_000430.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.225

Publications

13 publications found

Variant links:

Genes affected

PAFAH1B1 (HGNC:8574): (platelet activating factor acetylhydrolase 1b regulatory subunit 1) This locus was identified as encoding a gene that when mutated or lost caused the lissencephaly associated with Miller-Dieker lissencephaly syndrome. This gene encodes the non-catalytic alpha subunit of the intracellular Ib isoform of platelet-activating factor acteylhydrolase, a heterotrimeric enzyme that specifically catalyzes the removal of the acetyl group at the SN-2 position of platelet-activating factor (identified as 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine). Two other isoforms of intracellular platelet-activating factor acetylhydrolase exist: one composed of multiple subunits, the other, a single subunit. In addition, a single-subunit isoform of this enzyme is found in serum. [provided by RefSeq, Apr 2009]

PAFAH1B1 Gene-Disease associations (from GenCC):

lissencephaly due to LIS1 mutation
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P

PAFAH1B1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 17-2670358-C-T is Benign according to our data. Variant chr17-2670358-C-T is described in ClinVar as [Benign]. Clinvar id is 159528.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAFAH1B1	NM_000430.4 link	c.568+27C>T		intron_variant	Intron 6 of 10	ENST00000397195.10	NP_000421.1	P43034-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAFAH1B1	ENST00000397195.10 link	c.568+27C>T		intron_variant	Intron 6 of 10	1	NM_000430.4	ENSP00000380378.4		P43034-1

Frequencies

GnomAD3 genomes

AF:

0.894

AC:

135943

AN:

152080

Hom.:

61002

Cov.:

show subpopulations

Gnomad AFR

AF:

0.799

Gnomad AMI

AF:

0.969

Gnomad AMR

AF:

0.924

Gnomad ASJ

AF:

0.956

Gnomad EAS

AF:

0.929

Gnomad SAS

AF:

0.901

Gnomad FIN

AF:

0.932

Gnomad MID

AF:

0.892

Gnomad NFE

AF:

0.931

Gnomad OTH

AF:

0.910

GnomAD2 exomes

AF:

0.918

AC:

230555

AN:

251250

AF XY:

0.919

show subpopulations

Gnomad AFR exome

AF:

0.796

Gnomad AMR exome

AF:

0.920

Gnomad ASJ exome

AF:

0.957

Gnomad EAS exome

AF:

0.940

Gnomad FIN exome

AF:

0.932

Gnomad NFE exome

AF:

0.930

Gnomad OTH exome

AF:

0.924

GnomAD4 exome

AF:

0.922

AC:

1324113

AN:

1435736

Hom.:

611181

Cov.:

AF XY:

0.922

AC XY:

660366

AN XY:

716068

show subpopulations

African (AFR)

AF:

0.799

AC:

26295

AN:

32924

American (AMR)

AF:

0.919

AC:

41061

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.958

AC:

24866

AN:

25968

East Asian (EAS)

AF:

0.907

AC:

35894

AN:

39590

South Asian (SAS)

AF:

0.896

AC:

76850

AN:

85736

European-Finnish (FIN)

AF:

0.933

AC:

49831

AN:

53402

Middle Eastern (MID)

AF:

0.900

AC:

5110

AN:

5680

European-Non Finnish (NFE)

AF:

0.928

AC:

1009610

AN:

1088262

Other (OTH)

AF:

0.918

AC:

54596

AN:

59486

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

4526

9053

13579

18106

22632

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.894

AC:

136039

AN:

152198

Hom.:

61041

Cov.:

AF XY:

0.896

AC XY:

66659

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.799

AC:

33168

AN:

41506

American (AMR)

AF:

0.925

AC:

14140

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.956

AC:

3318

AN:

3472

East Asian (EAS)

AF:

0.928

AC:

4807

AN:

5180

South Asian (SAS)

AF:

0.899

AC:

4335

AN:

4820

European-Finnish (FIN)

AF:

0.932

AC:

9861

AN:

10584

Middle Eastern (MID)

AF:

0.891

AC:

262

AN:

294

European-Non Finnish (NFE)

AF:

0.931

AC:

63339

AN:

68022

Other (OTH)

AF:

0.911

AC:

1925

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

723

1446

2168

2891

3614

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.920

Hom.:

84969

Bravo

AF:

0.889

Asia WGS

AF:

0.917

AC:

3189

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 19, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Lissencephaly due to LIS1 mutation

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.3

(source)

DANN

Benign

0.49

PhyloP100

-0.23

PromoterAI

-0.0054

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

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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17-2670358-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over