NM_000430.4:c.-191+19575G>A

Variant names:

• chr17-2613581-G-A
• rs554857059
• NM_000430.4:c.-191+19575G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000430.4(PAFAH1B1):​c.-191+19575G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000525 in 281,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00056 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00048 (0 hom.)
• Consequence: PAFAH1B1 NM_000430.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.697
• 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]

SAMD11P1 (HGNC:44473): (sterile alpha motif domain containing 11 pseudogene 1)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 17-2613581-G-A is Benign according to our data. Variant chr17-2613581-G-A is described in ClinVar as [Benign]. Clinvar id is 2647220.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000565 (86/152298) while in subpopulation SAS AF = 0.0029 (14/4832). AF 95% confidence interval is 0.00175. There are 0 homozygotes in GnomAd4. There are 32 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 86 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAFAH1B1	NM_000430.4	c.-191+19575G>A		intron_variant	Intron 1 of 10	ENST00000397195.10	NP_000421.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAFAH1B1	ENST00000397195.10	c.-191+19575G>A		intron_variant	Intron 1 of 10	1	NM_000430.4	ENSP00000380378.4

Frequencies

GnomAD3 genomes AF: 0.000565 AC: 86 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00289

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000823

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.000479 AC: 62 AN: 129504 Hom.: 0 Cov.: 0 AF XY: 0.000558 AC XY: 38 AN XY: 68134

African (AFR) AF: 0.00 AC: 0 AN: 3072

American (AMR) AF: 0.00 AC: 0 AN: 6376

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3582

East Asian (EAS) AF: 0.00 AC: 0 AN: 7762

South Asian (SAS) AF: 0.00455 AC: 21 AN: 4614

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 638

European-Non Finnish (NFE) AF: 0.000514 AC: 37 AN: 71916

Other (OTH) AF: 0.000553 AC: 4 AN: 7232

GnomAD4 genome AF: 0.000565 AC: 86 AN: 152298 Hom.: 0 Cov.: 32 AF XY: 0.000430 AC XY: 32 AN XY: 74472

African (AFR) AF: 0.000144 AC: 6 AN: 41574

American (AMR) AF: 0.000392 AC: 6 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4832

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000824 AC: 56 AN: 68000

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000635 Hom.: 0

Bravo AF: 0.000412

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PAFAH1B1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.3
DANN	Benign	0.48
PhyloP100		0.70
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs554857059; hg19: chr17-2516875;