17-2597781-A-AGT

Position:

• chr17-2597781-A-AGT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000430.4(PAFAH1B1):​c.-191+3792_-191+3793dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.28 (6034 hom., cov: 0)
• Consequence: PAFAH1B1 NM_000430.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.890

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 17-2597781-A-AGT is Benign according to our data. Variant chr17-2597781-A-AGT is described in ClinVar as [Benign]. Clinvar id is 1294915.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAFAH1B1	NM_000430.4	c.-191+3792_-191+3793dup		intron_variant		ENST00000397195.10	NP_000421.1
PAFAH1B1	XM_011523901.3	c.-191+3792_-191+3793dup		intron_variant			XP_011522203.1
PAFAH1B1	XM_011523902.4	c.-396+3404_-396+3405dup		intron_variant			XP_011522204.1
PAFAH1B1	XM_017024701.2	c.-191+4468_-191+4469dup		intron_variant			XP_016880190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAFAH1B1	ENST00000397195.10	c.-191+3792_-191+3793dup		intron_variant		1	NM_000430.4	ENSP00000380378	P1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42251 AN: 150702 Hom.: 6031 Cov.: 0

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.255

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.280 AC: 42266 AN: 150816 Hom.: 6034 Cov.: 0 AF XY: 0.273 AC XY: 20075 AN XY: 73616

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.251

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs142241253; hg19: chr17-2501075;