rs3213696

Variant names:

• chr17-2670358-C-T
• rs3213696
• NM_000430.4:c.568+27C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-2670358-C-T
• chr17-2670358-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000430.4(PAFAH1B1):​c.568+27C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.92 in 1,587,934 control chromosomes in the GnomAD database, including 672,222 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.89 (61041 hom., cov: 31)
  • Exomes 𝑓: 0.92 (611181 hom.)
• Consequence: PAFAH1B1 NM_000430.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.225
• Publications: 13 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-2670358-C-T is Benign according to our data. Variant chr17-2670358-C-T is described in ClinVar as Benign. ClinVar VariationId is 159528.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.925 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.568+27C>T		intron	N/A	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.568+27C>T		intron	N/A	ENSP00000380378.4	P43034-1
	PAFAH1B1	ENST00000572915.6	TSL:1	n.536+27C>T		intron	N/A
	PAFAH1B1	ENST00000674608.1		c.622+27C>T		intron	N/A	ENSP00000501976.1	A0A6Q8PFU3

Frequencies

GnomAD3 genomes AF: 0.894 AC: 135943 AN: 152080 Hom.: 61002 Cov.: 31

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.969

Gnomad AMR AF: 0.924

Gnomad ASJ AF: 0.956

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.901

Gnomad FIN AF: 0.932

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.931

Gnomad OTH AF: 0.910

GnomAD2 exomes AF: 0.918 AC: 230555 AN: 251250 AF XY: 0.919

Gnomad AFR exome AF: 0.796

Gnomad AMR exome AF: 0.920

Gnomad ASJ exome AF: 0.957

Gnomad EAS exome AF: 0.940

Gnomad FIN exome AF: 0.932

Gnomad NFE exome AF: 0.930

Gnomad OTH exome AF: 0.924

GnomAD4 exome AF: 0.922 AC: 1324113 AN: 1435736 Hom.: 611181 Cov.: 26 AF XY: 0.922 AC XY: 660366 AN XY: 716068

African (AFR) AF: 0.799 AC: 26295 AN: 32924

American (AMR) AF: 0.919 AC: 41061 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.958 AC: 24866 AN: 25968

East Asian (EAS) AF: 0.907 AC: 35894 AN: 39590

South Asian (SAS) AF: 0.896 AC: 76850 AN: 85736

European-Finnish (FIN) AF: 0.933 AC: 49831 AN: 53402

Middle Eastern (MID) AF: 0.900 AC: 5110 AN: 5680

European-Non Finnish (NFE) AF: 0.928 AC: 1009610 AN: 1088262

Other (OTH) AF: 0.918 AC: 54596 AN: 59486

GnomAD4 genome AF: 0.894 AC: 136039 AN: 152198 Hom.: 61041 Cov.: 31 AF XY: 0.896 AC XY: 66659 AN XY: 74412

African (AFR) AF: 0.799 AC: 33168 AN: 41506

American (AMR) AF: 0.925 AC: 14140 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.956 AC: 3318 AN: 3472

East Asian (EAS) AF: 0.928 AC: 4807 AN: 5180

South Asian (SAS) AF: 0.899 AC: 4335 AN: 4820

European-Finnish (FIN) AF: 0.932 AC: 9861 AN: 10584

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.931 AC: 63339 AN: 68022

Other (OTH) AF: 0.911 AC: 1925 AN: 2114

Alfa AF: 0.920 Hom.: 84969

Bravo AF: 0.889

Asia WGS AF: 0.917 AC: 3189 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Lissencephaly due to LIS1 mutation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.3
DANN	Benign	0.49
PhyloP100		-0.23
PromoterAI		-0.0054	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs3213696; hg19: chr17-2573652; COSMIC: COSV68210095; COSMIC: COSV68210095;