Genetic Variant PAFAH1B2:c.411+121T>C (chr11-117164013-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002572.4(PAFAH1B2):c.411+121T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 964,624 control chromosomes in the GnomAD database, including 234,312 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.61 ( 30985 hom., cov: 32)

Exomes 𝑓: 0.70 ( 203327 hom. )

Consequence

PAFAH1B2
NM_002572.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.184

Publications

24 publications found

Variant links:

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]

PAFAH1B2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002572.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PAFAH1B2	NM_002572.4	MANE Select	c.411+121T>C	intron	N/A	NP_002563.1
PAFAH1B2	NM_001184746.2		c.411+121T>C	intron	N/A	NP_001171675.1
PAFAH1B2	NM_001309431.2		c.267+121T>C	intron	N/A	NP_001296360.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PAFAH1B2	ENST00000527958.6	TSL:1 MANE Select	c.411+121T>C	intron	N/A	ENSP00000435289.1
PAFAH1B2	ENST00000530272.1	TSL:1	c.411+121T>C	intron	N/A	ENSP00000431365.1
PAFAH1B2	ENST00000304808.10	TSL:1	c.249+121T>C	intron	N/A	ENSP00000304006.6

Frequencies

GnomAD3 genomes

AF:

0.614

AC:

93234

AN:

151914

Hom.:

30983

Cov.:

show subpopulations

Gnomad AFR

AF:

0.374

Gnomad AMI

AF:

0.943

Gnomad AMR

AF:

0.655

Gnomad ASJ

AF:

0.666

Gnomad EAS

AF:

0.375

Gnomad SAS

AF:

0.436

Gnomad FIN

AF:

0.695

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.760

Gnomad OTH

AF:

0.642

GnomAD4 exome

AF:

0.697

AC:

566512

AN:

812592

Hom.:

203327

Cov.:

AF XY:

0.690

AC XY:

289754

AN XY:

419732

show subpopulations

African (AFR)

AF:

0.363

AC:

7158

AN:

19722

American (AMR)

AF:

0.667

AC:

21305

AN:

31962

Ashkenazi Jewish (ASJ)

AF:

0.661

AC:

11624

AN:

17586

East Asian (EAS)

AF:

0.384

AC:

13937

AN:

36316

South Asian (SAS)

AF:

0.461

AC:

27483

AN:

59576

European-Finnish (FIN)

AF:

0.707

AC:

33478

AN:

47342

Middle Eastern (MID)

AF:

0.594

AC:

2539

AN:

4272

European-Non Finnish (NFE)

AF:

0.759

AC:

423283

AN:

557520

Other (OTH)

AF:

0.671

AC:

25705

AN:

38296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

7525

15051

22576

30102

37627

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7136

14272

21408

28544

35680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.613

AC:

93257

AN:

152032

Hom.:

30985

Cov.:

AF XY:

0.606

AC XY:

45013

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.374

AC:

15495

AN:

41448

American (AMR)

AF:

0.654

AC:

9975

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.666

AC:

2310

AN:

3470

East Asian (EAS)

AF:

0.375

AC:

1936

AN:

5158

South Asian (SAS)

AF:

0.437

AC:

2105

AN:

4814

European-Finnish (FIN)

AF:

0.695

AC:

7359

AN:

10594

Middle Eastern (MID)

AF:

0.633

AC:

186

AN:

294

European-Non Finnish (NFE)

AF:

0.760

AC:

51688

AN:

67980

Other (OTH)

AF:

0.638

AC:

1343

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1624

3248

4873

6497

8121

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

752

1504

2256

3008

3760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.707

Hom.:

56824

Bravo

AF:

0.604

Asia WGS

AF:

0.408

AC:

1420

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

2.1

(source)

DANN

Benign

0.30

PhyloP100

-0.18

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over