chr17-2595599-G-T

Position:

• chr17-2595599-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.648

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 -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
PAFAH1B1	NM_000430.4	c.-191+1593G>T		intron_variant		ENST00000397195.10	NP_000421.1
PAFAH1B1	XM_011523901.3	c.-191+1593G>T		intron_variant			XP_011522203.1
PAFAH1B1	XM_011523902.4	c.-396+1205G>T		intron_variant			XP_011522204.1
PAFAH1B1	XM_017024701.2	c.-191+2269G>T		intron_variant			XP_016880190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAFAH1B1	ENST00000397195.10	c.-191+1593G>T		intron_variant		1	NM_000430.4	ENSP00000380378	P1

Frequencies

GnomAD3 genomes AF: 0.00601 AC: 914 AN: 152088 Hom.: 17 Cov.: 31

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

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

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 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

Other links and lift over

dbSNP: rs76667110; hg19: chr17-2498893;