rs17160349

Positions:

• chr19-8262060-G-A
• chr19-8262060-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000251363.10(CERS4):​c.1136G>A​(p.Arg379Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,532,672 control chromosomes in the GnomAD database, including 19,096 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 0.15 (1707 hom., cov: 34)
  • Exomes 𝑓: 0.16 (17389 hom.)
• Consequence: CERS4 ENST00000251363.10 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.886

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004725814).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CERS4	NM_024552.3	c.1136G>A	p.Arg379Gln	missense_variant	12/12	ENST00000251363.10	NP_078828.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CERS4	ENST00000251363.10	c.1136G>A	p.Arg379Gln	missense_variant	12/12	1	NM_024552.3	ENSP00000251363	P1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22336 AN: 152194 Hom.: 1704 Cov.: 34

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.0819

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.156

GnomAD3 exomes AF: 0.156 AC: 27250 AN: 174770 Hom.: 2336 AF XY: 0.152 AC XY: 14392 AN XY: 94814

Gnomad AFR exome AF: 0.131

Gnomad AMR exome AF: 0.264

Gnomad ASJ exome AF: 0.156

Gnomad EAS exome AF: 0.0775

Gnomad SAS exome AF: 0.119

Gnomad FIN exome AF: 0.145

Gnomad NFE exome AF: 0.157

Gnomad OTH exome AF: 0.152

GnomAD4 exome AF: 0.156 AC: 215347 AN: 1380360 Hom.: 17389 Cov.: 35 AF XY: 0.155 AC XY: 105453 AN XY: 679634

Gnomad4 AFR exome AF: 0.129

Gnomad4 AMR exome AF: 0.245

Gnomad4 ASJ exome AF: 0.148

Gnomad4 EAS exome AF: 0.0801

Gnomad4 SAS exome AF: 0.127

Gnomad4 FIN exome AF: 0.144

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.152

GnomAD4 genome AF: 0.147 AC: 22342 AN: 152312 Hom.: 1707 Cov.: 34 AF XY: 0.144 AC XY: 10704 AN XY: 74474

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.0821

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.154

Alfa AF: 0.159 Hom.: 2650

Bravo AF: 0.153

TwinsUK AF: 0.164 AC: 607

ALSPAC AF: 0.160 AC: 615

ESP6500AA AF: 0.127 AC: 551

ESP6500EA AF: 0.156 AC: 1323

ExAC AF: 0.150 AC: 17950

Asia WGS AF: 0.0990 AC: 343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;T;T;T
Eigen	Benign	0.047
Eigen_PC	Benign	-0.056
FATHMM_MKL	Benign	0.62	D
LIST_S2	Uncertain	0.87	D;.;D;D
MetaRNN	Benign	0.0047	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	.;M;M;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.2	N;N;N;N
REVEL	Benign	0.085
Sift	Benign	0.097	T;T;T;D
Sift4G	Benign	0.12	T;T;T;D
Polyphen		1.0	.;D;D;.
Vest4		0.081
MPC		0.35
ClinPred		0.031	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.18

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

Other links and lift over

dbSNP: rs17160349; hg19: chr19-8326944; COSMIC: COSV52165848; COSMIC: COSV52165848;