17-2595599-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000430.4(PAFAH1B1):​c.-191+1593G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00601 in 152,206 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0060 ( 17 hom., cov: 31)

Consequence

PAFAH1B1
NM_000430.4 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.648
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 17-2595599-G-T is Benign according to our data. Variant chr17-2595599-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1326006.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0503 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PAFAH1B1NM_000430.4 linkuse as main transcriptc.-191+1593G>T intron_variant ENST00000397195.10 NP_000421.1
PAFAH1B1XM_011523901.3 linkuse as main transcriptc.-191+1593G>T intron_variant XP_011522203.1
PAFAH1B1XM_011523902.4 linkuse as main transcriptc.-396+1205G>T intron_variant XP_011522204.1
PAFAH1B1XM_017024701.2 linkuse as main transcriptc.-191+2269G>T intron_variant XP_016880190.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PAFAH1B1ENST00000397195.10 linkuse as main transcriptc.-191+1593G>T intron_variant 1 NM_000430.4 ENSP00000380378 P1P43034-1

Frequencies

GnomAD3 genomes
AF:
0.00601
AC:
914
AN:
152088
Hom.:
17
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000748
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0220
Gnomad ASJ
AF:
0.00634
Gnomad EAS
AF:
0.0551
Gnomad SAS
AF:
0.00538
Gnomad FIN
AF:
0.0114
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00121
Gnomad OTH
AF:
0.00478
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.00601
AC:
915
AN:
152206
Hom.:
17
Cov.:
31
AF XY:
0.00705
AC XY:
525
AN XY:
74420
show subpopulations
Gnomad4 AFR
AF:
0.000746
Gnomad4 AMR
AF:
0.0219
Gnomad4 ASJ
AF:
0.00634
Gnomad4 EAS
AF:
0.0556
Gnomad4 SAS
AF:
0.00539
Gnomad4 FIN
AF:
0.0114
Gnomad4 NFE
AF:
0.00121
Gnomad4 OTH
AF:
0.00473
Alfa
AF:
0.00296
Hom.:
1
Bravo
AF:
0.00755
Asia WGS
AF:
0.0270
AC:
92
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxMay 20, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.75
CADD
Benign
11
DANN
Benign
0.48

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs76667110; hg19: chr17-2498893; API