17-2666002-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000430.4(PAFAH1B1):​c.118-14T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,476,616 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0043 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00072 ( 3 hom. )

Consequence

PAFAH1B1
NM_000430.4 splice_polypyrimidine_tract, intron

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.164
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 -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 17-2666002-T-C is Benign according to our data. Variant chr17-2666002-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 256109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-2666002-T-C is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00429 (654/152306) while in subpopulation AFR AF= 0.0136 (566/41562). AF 95% confidence interval is 0.0127. There are 1 homozygotes in gnomad4. There are 293 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 654 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PAFAH1B1NM_000430.4 linkuse as main transcriptc.118-14T>C splice_polypyrimidine_tract_variant, intron_variant ENST00000397195.10 NP_000421.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PAFAH1B1ENST00000397195.10 linkuse as main transcriptc.118-14T>C splice_polypyrimidine_tract_variant, intron_variant 1 NM_000430.4 ENSP00000380378 P1P43034-1

Frequencies

GnomAD3 genomes
AF:
0.00428
AC:
651
AN:
152188
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0136
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.00393
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.000235
Gnomad OTH
AF:
0.00383
GnomAD3 exomes
AF:
0.00133
AC:
237
AN:
178042
Hom.:
1
AF XY:
0.00104
AC XY:
100
AN XY:
95894
show subpopulations
Gnomad AFR exome
AF:
0.0134
Gnomad AMR exome
AF:
0.00194
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000851
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000466
Gnomad OTH exome
AF:
0.00189
GnomAD4 exome
AF:
0.000720
AC:
954
AN:
1324310
Hom.:
3
Cov.:
28
AF XY:
0.000680
AC XY:
445
AN XY:
653948
show subpopulations
Gnomad4 AFR exome
AF:
0.0130
Gnomad4 AMR exome
AF:
0.00263
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000648
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000316
Gnomad4 OTH exome
AF:
0.00204
GnomAD4 genome
AF:
0.00429
AC:
654
AN:
152306
Hom.:
1
Cov.:
32
AF XY:
0.00393
AC XY:
293
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.0136
Gnomad4 AMR
AF:
0.00392
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000235
Gnomad4 OTH
AF:
0.00379
Alfa
AF:
0.00333
Hom.:
0
Bravo
AF:
0.00511
Asia WGS
AF:
0.00115
AC:
4
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Likely benign, criteria provided, single submitterclinical testingGeneDxFeb 16, 2018This 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. -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 28, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
2.2
DANN
Benign
0.66

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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: rs147692085; hg19: chr17-2569296; API