Genetic Variant PAFAH1B1:c.-191+3792_-191+3793dupGT (chr17-2597781-A-AGT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000430.4(PAFAH1B1):c.-191+3792_-191+3793dupGT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.28 ( 6034 hom., cov: 0)

Consequence

PAFAH1B1
NM_000430.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.890

Publications

0 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 -10 ACMG points.

BP6

Variant 17-2597781-A-AGT is Benign according to our data. Variant chr17-2597781-A-AGT is described in ClinVar as [Benign]. Clinvar id is 1294915.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PAFAH1B1	NM_000430.4 link	c.-191+3792_-191+3793dupGT	intron_variant	Intron 1 of 10	ENST00000397195.10	NP_000421.1	P43034-1
PAFAH1B1	XM_011523901.3 link	c.-191+3792_-191+3793dupGT	intron_variant	Intron 1 of 11		XP_011522203.1	A0A6Q8PFU3
PAFAH1B1	XM_011523902.4 link	c.-396+3404_-396+3405dupGT	intron_variant	Intron 1 of 12		XP_011522204.1	A0A6Q8PFU3
PAFAH1B1	XM_017024701.2 link	c.-191+4468_-191+4469dupGT	intron_variant	Intron 1 of 10		XP_016880190.1	P43034-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAFAH1B1	ENST00000397195.10 link	c.-191+3775_-191+3776insGT		intron_variant	Intron 1 of 10	1	NM_000430.4	ENSP00000380378.4		P43034-1

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

42251

AN:

150702

Hom.:

6031

Cov.:

show subpopulations

Gnomad AFR

AF:

0.269

Gnomad AMI

AF:

0.358

Gnomad AMR

AF:

0.241

Gnomad ASJ

AF:

0.280

Gnomad EAS

AF:

0.119

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.236

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.318

Gnomad OTH

AF:

0.255

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

GnomAD4 genome

AF:

0.280

AC:

42266

AN:

150816

Hom.:

6034

Cov.:

AF XY:

0.273

AC XY:

20075

AN XY:

73616

show subpopulations

African (AFR)

AF:

0.269

AC:

11051

AN:

41078

American (AMR)

AF:

0.241

AC:

3629

AN:

15050

Ashkenazi Jewish (ASJ)

AF:

0.280

AC:

966

AN:

3450

East Asian (EAS)

AF:

0.120

AC:

616

AN:

5136

South Asian (SAS)

AF:

0.226

AC:

1083

AN:

4790

European-Finnish (FIN)

AF:

0.236

AC:

2442

AN:

10332

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.318

AC:

21529

AN:

67698

Other (OTH)

AF:

0.251

AC:

524

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1427

2853

4280

5706

7133

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0873

Hom.:

208

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 14, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.89

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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17-2597781-A-AGT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over