17-2597798-GTC-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.842

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]

ACMG classification

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 GnomAd at 432 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAFAH1B1	NM_000430.4	c.-191+3794_-191+3795del		intron_variant		ENST00000397195.10
PAFAH1B1	XM_011523901.3	c.-191+3794_-191+3795del		intron_variant
PAFAH1B1	XM_011523902.4	c.-396+3406_-396+3407del		intron_variant
PAFAH1B1	XM_017024701.2	c.-191+4470_-191+4471del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAFAH1B1	ENST00000397195.10	c.-191+3794_-191+3795del		intron_variant		1	NM_000430.4	P1

Frequencies

GnomAD3 genomes AF: 0.00304 AC: 432 AN: 142038 Hom.: 9 Cov.: 30

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

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

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs746390038; hg19: chr17-2501092;