17-2593657-C-CGGAGCT

Variant names:

• chr17-2593657-C-CGGAGCT
• rs538397985
• NM_000430.4:c.-534_-529dupTGGAGC

Variant summary

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

The NM_000430.4(PAFAH1B1):​c.-534_-529dupTGGAGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0295 in 272,760 control chromosomes in the GnomAD database, including 644 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.051 (619 hom., cov: 30)
  • Exomes 𝑓: 0.0030 (25 hom.)
• Consequence: PAFAH1B1 NM_000430.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.33
• 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 17-2593657-C-CGGAGCT is Benign according to our data. Variant chr17-2593657-C-CGGAGCT is described in ClinVar as Benign. ClinVar VariationId is 322244.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 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.-534_-529dupTGGAGC		5_prime_UTR	Exon 1 of 11	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.-534_-529dupTGGAGC		5_prime_UTR	Exon 1 of 11	ENSP00000380378.4	P43034-1
	PAFAH1B1	ENST00000863847.1		c.-662_-657dupTGGAGC		5_prime_UTR	Exon 1 of 12	ENSP00000533906.1
	PAFAH1B1	ENST00000863848.1		c.-668_-663dupTGGAGC		5_prime_UTR	Exon 1 of 12	ENSP00000533907.1

Frequencies

GnomAD3 genomes AF: 0.0510 AC: 7683 AN: 150592 Hom.: 616 Cov.: 30

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0230

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000392

Gnomad SAS AF: 0.0316

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.000875

Gnomad OTH AF: 0.0362

GnomAD4 exome AF: 0.00297 AC: 363 AN: 122062 Hom.: 25 AF XY: 0.00273 AC XY: 186 AN XY: 68068

African (AFR) AF: 0.0779 AC: 217 AN: 2786

American (AMR) AF: 0.00613 AC: 19 AN: 3098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4188

East Asian (EAS) AF: 0.00 AC: 0 AN: 10166

South Asian (SAS) AF: 0.0160 AC: 64 AN: 3998

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6910

Middle Eastern (MID) AF: 0.00163 AC: 1 AN: 614

European-Non Finnish (NFE) AF: 0.000193 AC: 16 AN: 82762

Other (OTH) AF: 0.00610 AC: 46 AN: 7540

GnomAD4 genome AF: 0.0510 AC: 7691 AN: 150698 Hom.: 619 Cov.: 30 AF XY: 0.0496 AC XY: 3653 AN XY: 73622

African (AFR) AF: 0.171 AC: 7051 AN: 41116

American (AMR) AF: 0.0230 AC: 349 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3434

East Asian (EAS) AF: 0.000393 AC: 2 AN: 5088

South Asian (SAS) AF: 0.0315 AC: 150 AN: 4768

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10368

Middle Eastern (MID) AF: 0.0172 AC: 5 AN: 290

European-Non Finnish (NFE) AF: 0.000875 AC: 59 AN: 67450

Other (OTH) AF: 0.0358 AC: 75 AN: 2096

Alfa AF: 0.00833 Hom.: 8

Asia WGS AF: 0.0180 AC: 61 AN: 3370

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Lissencephaly/Subcortical Band Heterotopia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3

Splicing

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

Other links and lift over

dbSNP: rs538397985; hg19: chr17-2496951; COSMIC: COSV107508247;