rs6628

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_000430.4(PAFAH1B1):c.*17C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,589,384 control chromosomes in the GnomAD database, including 45,961 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3240 hom., cov: 32)

Exomes 𝑓: 0.24 ( 42721 hom. )

Consequence

PAFAH1B1
NM_000430.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: 3.27

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 17-2681819-C-T is Benign according to our data. Variant chr17-2681819-C-T is described in ClinVar as Benign. ClinVar VariationId is 42175.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAFAH1B1	NM_000430.4 link	c.*17C>T		3_prime_UTR_variant	Exon 11 of 11	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.*17C>T		3_prime_UTR_variant	Exon 11 of 11	1	NM_000430.4	ENSP00000380378.4		P43034-1

Frequencies

GnomAD3 genomes

AF:

0.198

AC:

30122

AN:

151862

Hom.:

3244

Cov.:

show subpopulations

Gnomad AFR

AF:

0.130

Gnomad AMI

AF:

0.326

Gnomad AMR

AF:

0.178

Gnomad ASJ

AF:

0.244

Gnomad EAS

AF:

0.0480

Gnomad SAS

AF:

0.136

Gnomad FIN

AF:

0.199

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.256

Gnomad OTH

AF:

0.185

GnomAD2 exomes

AF:

0.200

AC:

49213

AN:

246630

AF XY:

0.202

show subpopulations

Gnomad AFR exome

AF:

0.128

Gnomad AMR exome

AF:

0.173

Gnomad ASJ exome

AF:

0.244

Gnomad EAS exome

AF:

0.0491

Gnomad FIN exome

AF:

0.195

Gnomad NFE exome

AF:

0.251

Gnomad OTH exome

AF:

0.211

GnomAD4 exome

AF:

0.237

AC:

341329

AN:

1437404

Hom.:

42721

Cov.:

AF XY:

0.235

AC XY:

168435

AN XY:

715806

show subpopulations

African (AFR)

AF:

0.125

AC:

4143

AN:

33100

American (AMR)

AF:

0.175

AC:

7753

AN:

44296

Ashkenazi Jewish (ASJ)

AF:

0.248

AC:

6431

AN:

25896

East Asian (EAS)

AF:

0.0396

AC:

1570

AN:

39602

South Asian (SAS)

AF:

0.154

AC:

13166

AN:

85374

European-Finnish (FIN)

AF:

0.195

AC:

10405

AN:

53272

Middle Eastern (MID)

AF:

0.199

AC:

822

AN:

4140

European-Non Finnish (NFE)

AF:

0.260

AC:

283770

AN:

1092220

Other (OTH)

AF:

0.223

AC:

13269

AN:

59504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

10445

20890

31336

41781

52226

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9326

18652

27978

37304

46630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.198

AC:

30123

AN:

151980

Hom.:

3240

Cov.:

AF XY:

0.193

AC XY:

14326

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.130

AC:

5387

AN:

41460

American (AMR)

AF:

0.178

AC:

2710

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.244

AC:

848

AN:

3470

East Asian (EAS)

AF:

0.0477

AC:

247

AN:

5176

South Asian (SAS)

AF:

0.136

AC:

656

AN:

4810

European-Finnish (FIN)

AF:

0.199

AC:

2093

AN:

10536

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.256

AC:

17422

AN:

67958

Other (OTH)

AF:

0.182

AC:

385

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1235

2470

3706

4941

6176

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

316

632

948

1264

1580

<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:

0.226

Hom.:

743

Bravo

AF:

0.194

Asia WGS

AF:

0.0950

AC:

332

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 26, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: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

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Lissencephaly due to LIS1 mutation

Other:1

GeneReviews

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

3.3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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