chr17-2597781-A-AGTGT

Variant names:

• chr17-2597781-A-AGTGT
• rs142241253
• NM_000430.4:c.-191+3790_-191+3793dupGTGT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_000430.4(PAFAH1B1):​c.-191+3790_-191+3793dupGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0069 (8 hom., cov: 0)
• Consequence: PAFAH1B1 NM_000430.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.890
• Publications: 0 publications found

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]

PAFAH1B1 Gene-Disease associations (from GenCC):

• lissencephaly due to LIS1 mutation

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0069 (1042/150956) while in subpopulation SAS AF = 0.0175 (84/4792). AF 95% confidence interval is 0.0145. There are 8 homozygotes in GnomAd4. There are 490 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1042 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAFAH1B1	NM_000430.4	c.-191+3790_-191+3793dupGTGT		intron_variant	Intron 1 of 10	ENST00000397195.10	NP_000421.1
PAFAH1B1	XM_011523901.3	c.-191+3790_-191+3793dupGTGT		intron_variant	Intron 1 of 11		XP_011522203.1
PAFAH1B1	XM_011523902.4	c.-396+3402_-396+3405dupGTGT		intron_variant	Intron 1 of 12		XP_011522204.1
PAFAH1B1	XM_017024701.2	c.-191+4466_-191+4469dupGTGT		intron_variant	Intron 1 of 10		XP_016880190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAFAH1B1	ENST00000397195.10	c.-191+3775_-191+3776insGTGT		intron_variant	Intron 1 of 10	1	NM_000430.4	ENSP00000380378.4

Frequencies

GnomAD3 genomes AF: 0.00689 AC: 1039 AN: 150842 Hom.: 8 Cov.: 0

Gnomad AFR AF: 0.00358

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00551

Gnomad ASJ AF: 0.00869

Gnomad EAS AF: 0.000582

Gnomad SAS AF: 0.0167

Gnomad FIN AF: 0.00155

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00964

Gnomad OTH AF: 0.0102

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

GnomAD4 genome AF: 0.00690 AC: 1042 AN: 150956 Hom.: 8 Cov.: 0 AF XY: 0.00665 AC XY: 490 AN XY: 73692

African (AFR) AF: 0.00357 AC: 147 AN: 41136

American (AMR) AF: 0.00551 AC: 83 AN: 15074

Ashkenazi Jewish (ASJ) AF: 0.00869 AC: 30 AN: 3452

East Asian (EAS) AF: 0.000584 AC: 3 AN: 5140

South Asian (SAS) AF: 0.0175 AC: 84 AN: 4792

European-Finnish (FIN) AF: 0.00155 AC: 16 AN: 10346

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00966 AC: 654 AN: 67730

Other (OTH) AF: 0.0101 AC: 21 AN: 2088

Alfa AF: 0.000954 Hom.: 208

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.89

Splicing

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

Other links and lift over

dbSNP: rs142241253; hg19: chr17-2501075;