17-2593657-C-CGGAGCT

Position:

• chr17-2593657-C-CGGAGCT

Variant summary

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

The NM_000430.4(PAFAH1B1):​c.-534_-529dup 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

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 17-2593657-C-CGGAGCT is Benign according to our data. Variant chr17-2593657-C-CGGAGCT is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAFAH1B1	NM_000430.4	c.-534_-529dup		5_prime_UTR_variant	1/11	ENST00000397195.10	NP_000421.1
PAFAH1B1	XM_011523901.3	c.-534_-529dup		5_prime_UTR_variant	1/12		XP_011522203.1
PAFAH1B1	XM_017024701.2	c.-191+333_-191+338dup		intron_variant			XP_016880190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAFAH1B1	ENST00000397195.10	c.-534_-529dup		5_prime_UTR_variant	1/11	1	NM_000430.4	ENSP00000380378	P1
PAFAH1B1	ENST00000576586.5	c.-191+333_-191+338dup		intron_variant		4		ENSP00000461087
PAFAH1B1	ENST00000676201.1	n.10_15dup		non_coding_transcript_exon_variant	1/5

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

Gnomad4 AFR exome AF: 0.0779

Gnomad4 AMR exome AF: 0.00613

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0160

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000193

Gnomad4 OTH exome AF: 0.00610

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

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.0230

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000393

Gnomad4 SAS AF: 0.0315

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000875

Gnomad4 OTH AF: 0.0358

Alfa AF: 0.00833 Hom.: 8

Asia WGS AF: 0.0180 AC: 61 AN: 3370

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Lissencephaly/Subcortical Band Heterotopia Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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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: rs538397985; hg19: chr17-2496951;