17-2597781-AGTGTGT-AGTGTGTGT

Variant names:

• chr17-2597781-A-AGT
• rs142241253
• NM_000430.4:c.-191+3792_-191+3793dupGT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000430.4(PAFAH1B1):​c.-191+3792_-191+3793dupGT 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
• 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: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000430.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAFAH1B1	NM_000430.4	MANE Select	c.-191+3792_-191+3793dupGT		intron	N/A	NP_000421.1	P43034-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAFAH1B1	ENST00000397195.10	TSL:1 MANE Select	c.-191+3775_-191+3776insGT		intron	N/A	ENSP00000380378.4	P43034-1
	PAFAH1B1	ENST00000572915.6	TSL:1	n.50+3775_50+3776insGT		intron	N/A
	PAFAH1B1	ENST00000674608.1		c.-191+3775_-191+3776insGT		intron	N/A	ENSP00000501976.1	A0A6Q8PFU3

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

African (AFR) AF: 0.269 AC: 11051 AN: 41078

American (AMR) AF: 0.241 AC: 3629 AN: 15050

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 966 AN: 3450

East Asian (EAS) AF: 0.120 AC: 616 AN: 5136

South Asian (SAS) AF: 0.226 AC: 1083 AN: 4790

European-Finnish (FIN) AF: 0.236 AC: 2442 AN: 10332

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21529 AN: 67698

Other (OTH) AF: 0.251 AC: 524 AN: 2086

Alfa AF: 0.0873 Hom.: 208

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.89
Mutation Taster		=100/0	polymorphism (auto)

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;