chr17-2597742-TTCTC-T

Position:

• chr17-2597742-TTCTC-T

Variant summary

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

The NM_000430.4(PAFAH1B1):​c.-191+3741_-191+3744del 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 (6171 hom., cov: 15)
• Consequence: PAFAH1B1 NM_000430.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00200

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 17-2597742-TTCTC-T is Benign according to our data. Variant chr17-2597742-TTCTC-T is described in ClinVar as [Benign]. Clinvar id is 1183503.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAFAH1B1	NM_000430.4	c.-191+3741_-191+3744del		intron_variant		ENST00000397195.10	NP_000421.1
PAFAH1B1	XM_011523901.3	c.-191+3741_-191+3744del		intron_variant			XP_011522203.1
PAFAH1B1	XM_011523902.4	c.-396+3353_-396+3356del		intron_variant			XP_011522204.1
PAFAH1B1	XM_017024701.2	c.-191+4417_-191+4420del		intron_variant			XP_016880190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAFAH1B1	ENST00000397195.10	c.-191+3741_-191+3744del		intron_variant		1	NM_000430.4	ENSP00000380378	P1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42706 AN: 151162 Hom.: 6169 Cov.: 15

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.256

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.282 AC: 42718 AN: 151280 Hom.: 6171 Cov.: 15 AF XY: 0.275 AC XY: 20346 AN XY: 73862

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.252

Alfa AF: 0.302 Hom.: 838

Bravo AF: 0.280

Asia WGS AF: 0.167 AC: 583 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs10606544; hg19: chr17-2501036;