2-168715100-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_203463.3(CERS6):c.709C>G(p.Leu237Val) variant causes a missense change. The variant allele was found at a frequency of 0.000989 in 1,612,512 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0053 (12 hom., cov: 32)
  • Exomes 𝑓: 0.00054 (2 hom.)
• Consequence: CERS6 NM_203463.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.89

Genes affected

CERS6 (HGNC:23826): (ceramide synthase 6) Enables sphingosine N-acyltransferase activity. Involved in ceramide biosynthetic process. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.019506484).
• BP6: Variant 2-168715100-C-G is Benign according to our data. Variant chr2-168715100-C-G is described in ClinVar as [Benign]. Clinvar id is 780837.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00533 (811/152224) while in subpopulation AFR AF= 0.0186 (771/41560). AF 95% confidence interval is 0.0175. There are 12 homozygotes in gnomad4. There are 375 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 810 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CERS6	NM_203463.3	c.709C>G	p.Leu237Val	missense_variant	7/10	ENST00000305747.11
CERS6	NM_001256126.2	c.709C>G	p.Leu237Val	missense_variant	7/11
CERS6	XM_017003749.3	c.286C>G	p.Leu96Val	missense_variant	4/8
CERS6	XM_005246440.6	c.133C>G	p.Leu45Val	missense_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CERS6	ENST00000305747.11	c.709C>G	p.Leu237Val	missense_variant	7/10	2	NM_203463.3	A1
CERS6	ENST00000392687.4	c.709C>G	p.Leu237Val	missense_variant	7/11	1		P4

Frequencies

GnomAD3 genomes AF: 0.00533 AC: 810 AN: 152106 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00135 AC: 338 AN: 250196 Hom.: 1 AF XY: 0.000962 AC XY: 130 AN XY: 135202

Gnomad AFR exome AF: 0.0190

Gnomad AMR exome AF: 0.000644

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000660

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000657

GnomAD4 exome AF: 0.000537 AC: 784 AN: 1460288 Hom.: 2 Cov.: 30 AF XY: 0.000405 AC XY: 294 AN XY: 726380

Gnomad4 AFR exome AF: 0.0196

Gnomad4 AMR exome AF: 0.000606

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000349

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000990

Gnomad4 OTH exome AF: 0.00141

GnomAD4 genome AF: 0.00533 AC: 811 AN: 152224 Hom.: 12 Cov.: 32 AF XY: 0.00504 AC XY: 375 AN XY: 74416

Gnomad4 AFR AF: 0.0186

Gnomad4 AMR AF: 0.00190

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00170 Hom.: 0

Bravo AF: 0.00603

ESP6500AA AF: 0.0170 AC: 75

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00154 AC: 187

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 24, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.14
Cadd	Benign	18
Dann	Uncertain	0.98
DEOGEN2	Benign	0.36	T;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.82	T;T
MetaRNN	Benign	0.020	T;T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	0.96	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.2	N;N
REVEL	Uncertain	0.38
Sift	Benign	0.65	T;T
Sift4G	Benign	0.79	T;T
Polyphen		0.053	B;.
Vest4		0.44
MVP		0.40
MPC		0.26
ClinPred		0.019	T
GERP RS		4.6
Varity_R		0.11
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs116510340; hg19: chr2-169571610; COSMIC: COSV99045225;