rs1002666

Positions:

• chr2-168621508-T-C

Variant summary

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

The NM_203463.3(CERS6):​c.408-9477T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 152,064 control chromosomes in the GnomAD database, including 7,866 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 0.30 (7866 hom., cov: 32)
• Consequence: CERS6 NM_203463.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CERS6	NM_203463.3	c.408-9477T>C		intron_variant		ENST00000305747.11	NP_982288.1
CERS6	NM_001256126.2	c.408-9477T>C		intron_variant			NP_001243055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CERS6	ENST00000305747.11	c.408-9477T>C		intron_variant		2	NM_203463.3	ENSP00000306579	A1
CERS6	ENST00000392687.4	c.408-9477T>C		intron_variant		1		ENSP00000376453	P4

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46003 AN: 151946 Hom.: 7853 Cov.: 32

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.267

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.303 AC: 46037 AN: 152064 Hom.: 7866 Cov.: 32 AF XY: 0.304 AC XY: 22618 AN XY: 74310

Gnomad4 AFR AF: 0.465

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.265

Alfa AF: 0.255 Hom.: 1944

Bravo AF: 0.298

Asia WGS AF: 0.315 AC: 1096 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.66

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: rs1002666; hg19: chr2-169478018;