17-2613291-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000430.4(PAFAH1B1):​c.-191+19285C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000193 in 212,642 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00014 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00031 ( 1 hom. )

Consequence

PAFAH1B1
NM_000430.4 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.544
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]
SAMD11P1 (HGNC:44473): (sterile alpha motif domain containing 11 pseudogene 1)

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=-0.66).
BP6
Variant 17-2613291-C-G is Benign according to our data. Variant chr17-2613291-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2647218.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000145 (22/152084) while in subpopulation SAS AF= 0.00332 (16/4816). AF 95% confidence interval is 0.00208. There are 1 homozygotes in gnomad4. There are 15 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 22 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PAFAH1B1NM_000430.4 linkuse as main transcriptc.-191+19285C>G 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.-191+19285C>G intron_variant 1 NM_000430.4 ENSP00000380378 P1P43034-1
SAMD11P1ENST00000571429.2 linkuse as main transcriptn.654G>C non_coding_transcript_exon_variant 1/1

Frequencies

GnomAD3 genomes
AF:
0.000145
AC:
22
AN:
151966
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00332
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.000957
GnomAD4 exome
AF:
0.000314
AC:
19
AN:
60558
Hom.:
1
Cov.:
0
AF XY:
0.000329
AC XY:
11
AN XY:
33462
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00406
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000374
Gnomad4 OTH exome
AF:
0.000873
GnomAD4 genome
AF:
0.000145
AC:
22
AN:
152084
Hom.:
1
Cov.:
32
AF XY:
0.000202
AC XY:
15
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00332
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.000947
Bravo
AF:
0.0000264
Asia WGS
AF:
0.000866
AC:
3
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 testingCeGaT Center for Human Genetics TuebingenFeb 01, 2023PAFAH1B1: BS1 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.66
CADD
Benign
8.9
DANN
Benign
0.63

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: rs577447220; hg19: chr17-2516585; API