rs6628

Positions:

• chr17-2681819-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_000430.4(PAFAH1B1):​c.*17C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,589,384 control chromosomes in the GnomAD database, including 45,961 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3240 hom., cov: 32)
  • Exomes 𝑓: 0.24 (42721 hom.)
• Consequence: PAFAH1B1 NM_000430.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6 O:1
• Conservation: PhyloP100: 3.27

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 17-2681819-C-T is Benign according to our data. Variant chr17-2681819-C-T is described in ClinVar as [Benign]. Clinvar id is 42175.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-2681819-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAFAH1B1	NM_000430.4	c.*17C>T		3_prime_UTR_variant	11/11	ENST00000397195.10	NP_000421.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAFAH1B1	ENST00000397195.10	c.*17C>T		3_prime_UTR_variant	11/11	1	NM_000430.4	ENSP00000380378	P1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30122 AN: 151862 Hom.: 3244 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.0480

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.185

GnomAD3 exomes AF: 0.200 AC: 49213 AN: 246630 Hom.: 5303 AF XY: 0.202 AC XY: 26862 AN XY: 133224

Gnomad AFR exome AF: 0.128

Gnomad AMR exome AF: 0.173

Gnomad ASJ exome AF: 0.244

Gnomad EAS exome AF: 0.0491

Gnomad SAS exome AF: 0.156

Gnomad FIN exome AF: 0.195

Gnomad NFE exome AF: 0.251

Gnomad OTH exome AF: 0.211

GnomAD4 exome AF: 0.237 AC: 341329 AN: 1437404 Hom.: 42721 Cov.: 26 AF XY: 0.235 AC XY: 168435 AN XY: 715806

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.175

Gnomad4 ASJ exome AF: 0.248

Gnomad4 EAS exome AF: 0.0396

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.195

Gnomad4 NFE exome AF: 0.260

Gnomad4 OTH exome AF: 0.223

GnomAD4 genome AF: 0.198 AC: 30123 AN: 151980 Hom.: 3240 Cov.: 32 AF XY: 0.193 AC XY: 14326 AN XY: 74284

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.0477

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.182

Alfa AF: 0.226 Hom.: 743

Bravo AF: 0.194

Asia WGS AF: 0.0950 AC: 332 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 26, 2014	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Lissencephaly due to LIS1 mutation Other:1

not provided, no classification provided

literature only

GeneReviews

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	14
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6628; hg19: chr17-2585113;