1-150966161-C-T

Variant names:

• chr1-150966161-C-T
• rs779228104
• NM_022075.5:c.1130G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_022075.5(CERS2):​c.1130G>A​(p.Arg377His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000373 in 1,610,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R377P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: CERS2 NM_022075.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132
• Publications: 1 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]

ENSG00000259357 (HGNC:58295):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04773733).
• BS2: High AC in GnomAdExome4 at 58 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERS2	NM_022075.5	c.1130G>A	p.Arg377His	missense_variant	Exon 11 of 11	ENST00000368954.10	NP_071358.1
CERS2	NM_181746.4	c.1130G>A	p.Arg377His	missense_variant	Exon 11 of 11		NP_859530.1
CERS2	XM_011509451.3	c.1190G>A	p.Arg397His	missense_variant	Exon 11 of 11		XP_011507753.1
CERS2	XM_011509452.4	c.1130G>A	p.Arg377His	missense_variant	Exon 11 of 11		XP_011507754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERS2	ENST00000368954.10	c.1130G>A	p.Arg377His	missense_variant	Exon 11 of 11	1	NM_022075.5	ENSP00000357950.5

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152120 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000404 AC: 1 AN: 247472 AF XY: 0.00000746

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000889

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000398 AC: 58 AN: 1458350 Hom.: 0 Cov.: 35 AF XY: 0.0000358 AC XY: 26 AN XY: 725648

African (AFR) AF: 0.0000301 AC: 1 AN: 33194

American (AMR) AF: 0.0000231 AC: 1 AN: 43292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26006

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.0000486 AC: 54 AN: 1111082

Other (OTH) AF: 0.0000166 AC: 1 AN: 60246

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152120 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74292

African (AFR) AF: 0.00 AC: 0 AN: 41408

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000594

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	17
DANN	Benign	0.80
DEOGEN2	Benign	0.074	T;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.73	T;.
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.048	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.20	N;N
PhyloP100		0.13
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.16	N;N
REVEL	Benign	0.029
Sift	Benign	0.23	T;T
Sift4G	Benign	0.20	T;T
Polyphen		0.0010	B;B
Vest4		0.082
MutPred		0.25		Loss of MoRF binding (P = 6e-04);Loss of MoRF binding (P = 6e-04);
MVP		0.13
MPC		0.72
ClinPred		0.10	T
GERP RS		-0.15
Varity_R		0.028
gMVP		0.30
Mutation Taster		=93/7	polymorphism

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: rs779228104; hg19: chr1-150938637; COSMIC: COSV99643874; COSMIC: COSV99643874;