Variant chr1-150968149-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022075.5(CERS2):c.344A>C(p.Glu115Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,609,316 control chromosomes in the GnomAD database, including 31,143 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.14 ( 2012 hom., cov: 32)

Exomes 𝑓: 0.19 ( 29131 hom. )

Consequence

CERS2
NM_022075.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.61

Variant links:

Genes affected

CERS2 (HGNC:14076): (ceramide synthase 2) This gene encodes a protein that has sequence similarity to yeast longevity assurance gene 1. Mutation or overexpression of the related gene in yeast has been shown to alter yeast lifespan. The human protein may play a role in the regulation of cell growth. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2008]

CERS2 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=0.001857996).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CERS2	NM_022075.5 linkuse as main transcript	c.344A>C	p.Glu115Ala	missense_variant	4/11	ENST00000368954.10
CERS2	NM_181746.4 linkuse as main transcript	c.344A>C	p.Glu115Ala	missense_variant	4/11
CERS2	XM_011509451.3 linkuse as main transcript	c.404A>C	p.Glu135Ala	missense_variant	4/11
CERS2	XM_011509452.4 linkuse as main transcript	c.344A>C	p.Glu115Ala	missense_variant	4/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CERS2	ENST00000368954.10 linkuse as main transcript	c.344A>C	p.Glu115Ala	missense_variant	4/11	1	NM_022075.5	P1

Frequencies

GnomAD3 genomes

AF:

0.142

AC:

21592

AN:

152074

Hom.:

2012

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0403

Gnomad AMI

AF:

0.286

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.198

Gnomad EAS

AF:

0.0271

Gnomad SAS

AF:

0.0679

Gnomad FIN

AF:

0.198

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.208

Gnomad OTH

AF:

0.148

GnomAD3 exomes

AF:

0.147

AC:

36447

AN:

247474

Hom.:

3308

AF XY:

0.148

AC XY:

19915

AN XY:

134190

show subpopulations

Gnomad AFR exome

AF:

0.0347

Gnomad AMR exome

AF:

0.0891

Gnomad ASJ exome

AF:

0.191

Gnomad EAS exome

AF:

0.0346

Gnomad SAS exome

AF:

0.0799

Gnomad FIN exome

AF:

0.192

Gnomad NFE exome

AF:

0.205

Gnomad OTH exome

AF:

0.172

GnomAD4 exome

AF:

0.192

AC:

279942

AN:

1457124

Hom.:

29131

Cov.:

AF XY:

0.189

AC XY:

137273

AN XY:

725172

show subpopulations

Gnomad4 AFR exome

AF:

0.0325

Gnomad4 AMR exome

AF:

0.0938

Gnomad4 ASJ exome

AF:

0.190

Gnomad4 EAS exome

AF:

0.0434

Gnomad4 SAS exome

AF:

0.0821

Gnomad4 FIN exome

AF:

0.190

Gnomad4 NFE exome

AF:

0.216

Gnomad4 OTH exome

AF:

0.179

GnomAD4 genome

AF:

0.142

AC:

21587

AN:

152192

Hom.:

2012

Cov.:

AF XY:

0.140

AC XY:

10430

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0401

Gnomad4 AMR

AF:

0.125

Gnomad4 ASJ

AF:

0.198

Gnomad4 EAS

AF:

0.0268

Gnomad4 SAS

AF:

0.0684

Gnomad4 FIN

AF:

0.198

Gnomad4 NFE

AF:

0.208

Gnomad4 OTH

AF:

0.147

Alfa

AF:

0.186

Hom.:

6838

Bravo

AF:

0.133

TwinsUK

AF:

0.211

AC:

783

ALSPAC

AF:

0.206

AC:

792

ESP6500AA

AF:

0.0399

AC:

176

ESP6500EA

AF:

0.212

AC:

1821

ExAC

AF:

0.147

AC:

17826

Asia WGS

AF:

0.0490

AC:

171

AN:

3478

EpiCase

AF:

0.207

EpiControl

AF:

0.199

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;D;.;D;D;D;D;D

MetaRNN

Benign

0.0019

T;T;T;T;T;T;T;T

MetaSVM

Pathogenic

0.82

MutationTaster

Benign

3.6e-7

P;P;P

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-4.7

D;D;D;.;D;D;D;D

Sift

Uncertain

0.0050

D;D;D;.;D;D;D;D

Sift4G

Uncertain

0.0080

D;D;D;.;.;.;.;.

Polyphen

0.86

.;P;P;.;.;.;.;.

Vest4

0.48

MPC

1.3

ClinPred

0.022

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.83

gMVP

0.69

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