17-2597798-GTC-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_000430.4(PAFAH1B1):​c.-191+3794_-191+3795del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00304 in 142,158 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0030 ( 9 hom., cov: 30)

Consequence

PAFAH1B1
NM_000430.4 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.842
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 -10 ACMG points.

BP6
Variant 17-2597798-GTC-G is Benign according to our data. Variant chr17-2597798-GTC-G is described in ClinVar as [Likely_benign]. Clinvar id is 1342740.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00304 (432/142158) while in subpopulation NFE AF= 0.00102 (65/63564). AF 95% confidence interval is 0.000823. There are 9 homozygotes in gnomad4. There are 317 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
High AC in GnomAd4 at 432 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PAFAH1B1NM_000430.4 linkuse as main transcriptc.-191+3794_-191+3795del intron_variant ENST00000397195.10 NP_000421.1
PAFAH1B1XM_011523901.3 linkuse as main transcriptc.-191+3794_-191+3795del intron_variant XP_011522203.1
PAFAH1B1XM_011523902.4 linkuse as main transcriptc.-396+3406_-396+3407del intron_variant XP_011522204.1
PAFAH1B1XM_017024701.2 linkuse as main transcriptc.-191+4470_-191+4471del 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+3794_-191+3795del intron_variant 1 NM_000430.4 ENSP00000380378 P1P43034-1

Frequencies

GnomAD3 genomes
AF:
0.00304
AC:
432
AN:
142038
Hom.:
9
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0000520
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000706
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000221
Gnomad FIN
AF:
0.0364
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00102
Gnomad OTH
AF:
0.00154
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.00304
AC:
432
AN:
142158
Hom.:
9
Cov.:
30
AF XY:
0.00457
AC XY:
317
AN XY:
69364
show subpopulations
Gnomad4 AFR
AF:
0.0000518
Gnomad4 AMR
AF:
0.0000705
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000221
Gnomad4 FIN
AF:
0.0364
Gnomad4 NFE
AF:
0.00102
Gnomad4 OTH
AF:
0.00152
Alfa
AF:
0.00263
Hom.:
1
Asia WGS
AF:
0.000577
AC:
2
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 testingGeneDxAug 30, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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: rs746390038; hg19: chr17-2501092; API