Variant 9-19409109-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001010887.3(ACER2):c.25C>A(p.Gln9Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000943 in 1,601,998 control chromosomes in the GnomAD database, including 13 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 0.0049 ( 8 hom., cov: 33)

Exomes 𝑓: 0.00052 ( 5 hom. )

Consequence

ACER2
NM_001010887.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.69

Variant links:

Genes affected

ACER2 (HGNC:23675): (alkaline ceramidase 2) The sphingolipid metabolite sphingosine-1-phosphate promotes cell proliferation and survival, whereas its precursor, sphingosine, has the opposite effect. The ceramidase ACER2 hydrolyzes very long chain ceramides to generate sphingosine (Xu et al., 2006 [PubMed 16940153]).[supplied by OMIM, Jul 2010]

ACER2 links:

ACER2 (HGNC:):

ACER2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008359581).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00495 (754/152324) while in subpopulation AFR AF= 0.0176 (731/41574). AF 95% confidence interval is 0.0165. There are 8 homozygotes in gnomad4. There are 361 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACER2	NM_001010887.3 linkuse as main transcript	c.25C>A	p.Gln9Lys	missense_variant	1/6	ENST00000340967.3	NP_001010887.2	Q5QJU3-1B3KVV5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACER2	ENST00000340967.3 linkuse as main transcript	c.25C>A	p.Gln9Lys	missense_variant	1/6	1	NM_001010887.3	ENSP00000342609.2		Q5QJU3-1

Frequencies

GnomAD3 genomes

AF:

0.00495

AC:

753

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0176

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00112

AC:

254

AN:

225856

Hom.:

AF XY:

0.000898

AC XY:

110

AN XY:

122540

show subpopulations

Gnomad AFR exome

AF:

0.0173

Gnomad AMR exome

AF:

0.000525

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000396

Gnomad OTH exome

AF:

0.000180

GnomAD4 exome

AF:

0.000521

AC:

756

AN:

1449674

Hom.:

Cov.:

AF XY:

0.000432

AC XY:

311

AN XY:

719858

show subpopulations

Gnomad4 AFR exome

AF:

0.0192

Gnomad4 AMR exome

AF:

0.000650

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000145

Gnomad4 OTH exome

AF:

0.00117

GnomAD4 genome

AF:

0.00495

AC:

754

AN:

152324

Hom.:

Cov.:

AF XY:

0.00485

AC XY:

361

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0176

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00301

Hom.:

Bravo

AF:

0.00595

ESP6500AA

AF:

0.0164

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.00145

AC:

175

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.17

Eigen

Benign

0.037

Eigen_PC

Benign

0.22

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

MetaRNN

Benign

0.0084

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.47

REVEL

Benign

0.10

Sift

Benign

0.54

Sift4G

Benign

0.89

Polyphen

0.038

Vest4

0.50

MVP

0.42

MPC

0.14

ClinPred

0.097

GERP RS

5.0

Varity_R

0.30

gMVP

0.89

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over