2-168505032-C-T

Position:

• chr2-168505032-C-T

Variant summary

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

The NM_203463.3(CERS6):​c.171-42564C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 151,758 control chromosomes in the GnomAD database, including 12,248 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 0.37 (12248 hom., cov: 30)
• Consequence: CERS6 NM_203463.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CERS6	NM_203463.3	c.171-42564C>T		intron_variant		ENST00000305747.11
CERS6	NM_001256126.2	c.171-42564C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CERS6	ENST00000305747.11	c.171-42564C>T		intron_variant		2	NM_203463.3	A1
CERS6	ENST00000392687.4	c.171-42564C>T		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56034 AN: 151640 Hom.: 12245 Cov.: 30

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.369 AC: 56048 AN: 151758 Hom.: 12248 Cov.: 30 AF XY: 0.377 AC XY: 27920 AN XY: 74124

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.542

Gnomad4 EAS AF: 0.641

Gnomad4 SAS AF: 0.640

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.400

Alfa AF: 0.436 Hom.: 30868

Bravo AF: 0.358

Asia WGS AF: 0.608 AC: 2116 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	1.9
DANN	Benign	0.63

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: rs12479292; hg19: chr2-169361542;