chr1-150968149-T-G

Variant names:

• chr1-150968149-T-G
• rs267738
• NM_022075.5:c.344A>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 1P and 12B. PP3 BP4_Strong BA1

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.

• Frequency:
  • Genomes: 𝑓 0.14 (2012 hom., cov: 32)
  • Exomes 𝑓: 0.19 (29131 hom.)
• Consequence: CERS2 NM_022075.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.61
• Publications: 99 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• PP3: Multiple lines of computational evidence support a deleterious effect 6: Cadd, FATHMM_MKL, phyloP100way_vertebrate, PROVEAN, REVEL, REVEL [when BayesDel_addAF, max_spliceai, MetaRNN, MutationTaster was below the threshold]
• 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 rank	MANE	Protein	UniProt
CERS2	NM_022075.5	c.344A>C	p.Glu115Ala	missense_variant	Exon 4 of 11	ENST00000368954.10	NP_071358.1
CERS2	NM_181746.4	c.344A>C	p.Glu115Ala	missense_variant	Exon 4 of 11		NP_859530.1
CERS2	XM_011509451.3	c.404A>C	p.Glu135Ala	missense_variant	Exon 4 of 11		XP_011507753.1
CERS2	XM_011509452.4	c.344A>C	p.Glu115Ala	missense_variant	Exon 4 of 11		XP_011507754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERS2	ENST00000368954.10	c.344A>C	p.Glu115Ala	missense_variant	Exon 4 of 11	1	NM_022075.5	ENSP00000357950.5

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21592 AN: 152074 Hom.: 2012 Cov.: 32

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

GnomAD2 exomes AF: 0.147 AC: 36447 AN: 247474 AF XY: 0.148

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 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.: 35 AF XY: 0.189 AC XY: 137273 AN XY: 725172

African (AFR) AF: 0.0325 AC: 1087 AN: 33476

American (AMR) AF: 0.0938 AC: 4193 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 4978 AN: 26132

East Asian (EAS) AF: 0.0434 AC: 1721 AN: 39696

South Asian (SAS) AF: 0.0821 AC: 7079 AN: 86256

European-Finnish (FIN) AF: 0.190 AC: 9275 AN: 48810

Middle Eastern (MID) AF: 0.161 AC: 927 AN: 5768

European-Non Finnish (NFE) AF: 0.216 AC: 239899 AN: 1111900

Other (OTH) AF: 0.179 AC: 10783 AN: 60364

GnomAD4 genome AF: 0.142 AC: 21587 AN: 152192 Hom.: 2012 Cov.: 32 AF XY: 0.140 AC XY: 10430 AN XY: 74402

African (AFR) AF: 0.0401 AC: 1667 AN: 41536

American (AMR) AF: 0.125 AC: 1907 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 687 AN: 3472

East Asian (EAS) AF: 0.0268 AC: 139 AN: 5184

South Asian (SAS) AF: 0.0684 AC: 330 AN: 4824

European-Finnish (FIN) AF: 0.198 AC: 2097 AN: 10586

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14152 AN: 67992

Other (OTH) AF: 0.147 AC: 310 AN: 2110

Alfa AF: 0.183 Hom.: 9459

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	T
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.85	.;D;D;.;.;.;.;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.99	D
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	D
MutationAssessor	Uncertain	2.6	.;M;M;.;.;.;.;.
PhyloP100		7.6
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-4.7	D;D;D;.;D;D;D;D
REVEL	Pathogenic	0.78
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	T
GERP RS		4.9
PromoterAI		-0.0051	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.83
gMVP		0.69
Mutation Taster		=89/11	polymorphism (auto)

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

Other links and lift over

dbSNP: rs267738; hg19: chr1-150940625; COSMIC: COSV107229501; COSMIC: COSV107229501;