rs17160349

Variant names:

• chr19-8262060-G-A
• rs17160349
• NM_024552.3:c.1136G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024552.3(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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (1707 hom., cov: 34)
  • Exomes 𝑓: 0.16 (17389 hom.)
• Consequence: CERS4 NM_024552.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.886
• Publications: 21 publications found

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]

ENSG00000303688 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CERS4	NM_024552.3	c.1136G>A	p.Arg379Gln	missense_variant	Exon 12 of 12	ENST00000251363.10	NP_078828.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERS4	ENST00000251363.10	c.1136G>A	p.Arg379Gln	missense_variant	Exon 12 of 12	1	NM_024552.3	ENSP00000251363.5

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

GnomAD2 exomes AF: 0.156 AC: 27250 AN: 174770 AF XY: 0.152

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 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

African (AFR) AF: 0.129 AC: 3941 AN: 30460

American (AMR) AF: 0.245 AC: 7276 AN: 29726

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 3091 AN: 20896

East Asian (EAS) AF: 0.0801 AC: 3121 AN: 38982

South Asian (SAS) AF: 0.127 AC: 9338 AN: 73646

European-Finnish (FIN) AF: 0.144 AC: 7109 AN: 49278

Middle Eastern (MID) AF: 0.158 AC: 842 AN: 5320

European-Non Finnish (NFE) AF: 0.160 AC: 172049 AN: 1075490

Other (OTH) AF: 0.152 AC: 8580 AN: 56562

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

African (AFR) AF: 0.127 AC: 5277 AN: 41580

American (AMR) AF: 0.181 AC: 2770 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 505 AN: 3472

East Asian (EAS) AF: 0.0821 AC: 425 AN: 5176

South Asian (SAS) AF: 0.113 AC: 548 AN: 4830

European-Finnish (FIN) AF: 0.141 AC: 1503 AN: 10622

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10858 AN: 68008

Other (OTH) AF: 0.154 AC: 325 AN: 2114

Alfa AF: 0.160 Hom.: 2950

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;.
PhyloP100		0.89
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
Mutation Taster		=99/1	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: rs17160349; hg19: chr19-8326944; COSMIC: COSV52165848; COSMIC: COSV52165848;