11-117171692-C-T

Variant names:

• chr11-117171692-C-T
• rs186808413
• ENST00000530272.1:c.482C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001184746.2(PAFAH1B2):​c.482C>T​(p.Ser161Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00928 in 1,535,014 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0069 (7 hom., cov: 31)
  • Exomes 𝑓: 0.0095 (79 hom.)
• Consequence: PAFAH1B2 NM_001184746.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.120
• Publications: 9 publications found

Genes affected

PAFAH1B2 (HGNC:8575): (platelet activating factor acetylhydrolase 1b catalytic subunit 2) Platelet-activating factor acetylhydrolase (PAFAH) inactivates platelet-activating factor (PAF) into acetate and LYSO-PAF. This gene encodes the beta subunit of PAFAH, the other subunits are alpha and gamma. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jan 2014]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0031649172).
• BP6: Variant 11-117171692-C-T is Benign according to our data. Variant chr11-117171692-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2672484.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 7 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001184746.2. 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
	PAFAH1B2	NM_001184746.2		c.482C>T	p.Ser161Leu	missense	Exon 6 of 7	NP_001171675.1	P68402-4
	PAFAH1B2	NM_001184747.2		c.412-4214C>T		intron	N/A	NP_001171676.1	P68402-2
	PAFAH1B2	NM_001184748.2		c.394-3201C>T		intron	N/A	NP_001171677.1	P68402-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAFAH1B2	ENST00000530272.1	TSL:1	c.482C>T	p.Ser161Leu	missense	Exon 6 of 7	ENSP00000431365.1	P68402-4
	PAFAH1B2	ENST00000529887.6	TSL:1	c.412-4214C>T		intron	N/A	ENSP00000434951.2	P68402-2
	PAFAH1B2	ENST00000419197.6	TSL:2	c.394-3201C>T		intron	N/A	ENSP00000388742.2	P68402-3

Frequencies

GnomAD3 genomes AF: 0.00692 AC: 1053 AN: 152118 Hom.: 7 Cov.: 31

Gnomad AFR AF: 0.00229

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00589

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00962

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.00573

GnomAD2 exomes AF: 0.00634 AC: 853 AN: 134536 AF XY: 0.00635

Gnomad AFR exome AF: 0.00155

Gnomad AMR exome AF: 0.00405

Gnomad ASJ exome AF: 0.00458

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00967

Gnomad NFE exome AF: 0.0109

Gnomad OTH exome AF: 0.00700

GnomAD4 exome AF: 0.00955 AC: 13199 AN: 1382778 Hom.: 79 Cov.: 30 AF XY: 0.00938 AC XY: 6401 AN XY: 682376

African (AFR) AF: 0.00184 AC: 58 AN: 31584

American (AMR) AF: 0.00431 AC: 154 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.00433 AC: 109 AN: 25174

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35728

South Asian (SAS) AF: 0.00179 AC: 142 AN: 79212

European-Finnish (FIN) AF: 0.00915 AC: 310 AN: 33882

Middle Eastern (MID) AF: 0.00791 AC: 45 AN: 5692

European-Non Finnish (NFE) AF: 0.0111 AC: 11930 AN: 1077944

Other (OTH) AF: 0.00778 AC: 450 AN: 57862

GnomAD4 genome AF: 0.00692 AC: 1053 AN: 152236 Hom.: 7 Cov.: 31 AF XY: 0.00634 AC XY: 472 AN XY: 74424

African (AFR) AF: 0.00229 AC: 95 AN: 41534

American (AMR) AF: 0.00589 AC: 90 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4818

European-Finnish (FIN) AF: 0.00962 AC: 102 AN: 10602

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0107 AC: 730 AN: 68014

Other (OTH) AF: 0.00567 AC: 12 AN: 2116

Alfa AF: 0.00927 Hom.: 11

Bravo AF: 0.00677

TwinsUK AF: 0.0113 AC: 42

ALSPAC AF: 0.0122 AC: 47

ExAC AF: 0.00339 AC: 56

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	10
DANN	Benign	0.83
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.38	T
MetaRNN	Benign	0.0032	T
MetaSVM	Benign	-0.98	T
PhyloP100		0.12
PROVEAN	Benign	1.9	N
REVEL	Benign	0.16
Sift	Benign	1.0	T
Sift4G	Benign	0.95	T
Vest4		0.11
MVP		0.068
ClinPred		0.0041	T
GERP RS		-0.025
Mutation Taster		=99/1	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs186808413; hg19: chr11-117042408;