chr2-168642804-A-G

Variant names:

• chr2-168642804-A-G
• rs6433083
• NM_203463.3:c.465+11762A>G

Variant summary

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

The NM_203463.3(CERS6):​c.465+11762A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,092 control chromosomes in the GnomAD database, including 8,994 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 0.31 (8994 hom., cov: 32)
• Consequence: CERS6 NM_203463.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERS6	NM_203463.3	c.465+11762A>G		intron_variant	Intron 4 of 9	ENST00000305747.11	NP_982288.1
CERS6	NM_001256126.2	c.465+11762A>G		intron_variant	Intron 4 of 10		NP_001243055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERS6	ENST00000305747.11	c.465+11762A>G		intron_variant	Intron 4 of 9	2	NM_203463.3	ENSP00000306579.6
CERS6	ENST00000392687.4	c.465+11762A>G		intron_variant	Intron 4 of 10	1		ENSP00000376453.4

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47235 AN: 151974 Hom.: 8979 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.311 AC: 47283 AN: 152092 Hom.: 8994 Cov.: 32 AF XY: 0.315 AC XY: 23438 AN XY: 74360

African (AFR) AF: 0.522 AC: 21648 AN: 41458

American (AMR) AF: 0.350 AC: 5355 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 647 AN: 3466

East Asian (EAS) AF: 0.297 AC: 1537 AN: 5168

South Asian (SAS) AF: 0.434 AC: 2094 AN: 4824

European-Finnish (FIN) AF: 0.195 AC: 2064 AN: 10588

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13151 AN: 67988

Other (OTH) AF: 0.273 AC: 578 AN: 2114

Alfa AF: 0.279 Hom.: 1305

Bravo AF: 0.328

Asia WGS AF: 0.361 AC: 1258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	13
DANN	Benign	0.68
PhyloP100		1.3
Mutation Taster		=100/0	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: rs6433083; hg19: chr2-169499314;