dbSNP rs11881630: CERS4:p.Ala82Ala (chr19-8254571-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_024552.3(CERS4):c.246C>T(p.Ala82Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0333 in 1,613,086 control chromosomes in the GnomAD database, including 2,362 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 0.075 ( 799 hom., cov: 31)

Exomes 𝑓: 0.029 ( 1563 hom. )

Consequence

CERS4
NM_024552.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.995

Publications

11 publications found

Variant links:

Genes affected

CERS4 (HGNC:23747): (ceramide synthase 4) Enables sphingosine N-acyltransferase activity. Involved in ceramide biosynthetic process. Predicted to be located in endoplasmic reticulum membrane. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

CERS4 links:

ENSG00000303688 (HGNC:):

ENSG00000303688 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP7

Synonymous conserved (PhyloP=-0.995 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERS4	NM_024552.3 link	c.246C>T	p.Ala82Ala	synonymous_variant	Exon 4 of 12	ENST00000251363.10	NP_078828.2	Q9HA82Q53HF9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERS4	ENST00000251363.10 link	c.246C>T	p.Ala82Ala	synonymous_variant	Exon 4 of 12	1	NM_024552.3	ENSP00000251363.5		Q9HA82

Frequencies

GnomAD3 genomes

AF:

0.0750

AC:

11412

AN:

152108

Hom.:

799

Cov.:

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.0487

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.0468

Gnomad FIN

AF:

0.0816

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0170

Gnomad OTH

AF:

0.0686

GnomAD2 exomes

AF:

0.0493

AC:

12291

AN:

249306

AF XY:

0.0454

show subpopulations

Gnomad AFR exome

AF:

0.184

Gnomad AMR exome

AF:

0.0396

Gnomad ASJ exome

AF:

0.00589

Gnomad EAS exome

AF:

0.148

Gnomad FIN exome

AF:

0.0769

Gnomad NFE exome

AF:

0.0170

Gnomad OTH exome

AF:

0.0466

GnomAD4 exome

AF:

0.0289

AC:

42232

AN:

1460860

Hom.:

1563

Cov.:

AF XY:

0.0287

AC XY:

20835

AN XY:

726676

show subpopulations

African (AFR)

AF:

0.180

AC:

6006

AN:

33450

American (AMR)

AF:

0.0422

AC:

1885

AN:

44620

Ashkenazi Jewish (ASJ)

AF:

0.00685

AC:

179

AN:

26122

East Asian (EAS)

AF:

0.147

AC:

5825

AN:

39652

South Asian (SAS)

AF:

0.0420

AC:

3617

AN:

86094

European-Finnish (FIN)

AF:

0.0728

AC:

3868

AN:

53112

Middle Eastern (MID)

AF:

0.0500

AC:

285

AN:

5698

European-Non Finnish (NFE)

AF:

0.0163

AC:

18142

AN:

1111748

Other (OTH)

AF:

0.0402

AC:

2425

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

2088

4175

6263

8350

10438

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0751

AC:

11428

AN:

152226

Hom.:

799

Cov.:

AF XY:

0.0779

AC XY:

5797

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.180

AC:

7485

AN:

41536

American (AMR)

AF:

0.0486

AC:

743

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00576

AC:

AN:

3470

East Asian (EAS)

AF:

0.147

AC:

759

AN:

5160

South Asian (SAS)

AF:

0.0456

AC:

220

AN:

4828

European-Finnish (FIN)

AF:

0.0816

AC:

866

AN:

10612

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0170

AC:

1157

AN:

68018

Other (OTH)

AF:

0.0674

AC:

142

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

516

1032

1549

2065

2581

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0404

Hom.:

170

Bravo

AF:

0.0802

Asia WGS

AF:

0.0950

AC:

329

AN:

3478

EpiCase

AF:

0.0165

EpiControl

AF:

0.0156

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.6

(source)

DANN

Benign

0.46

PhyloP100

-0.99

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs11881630

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over