rs13393173

Positions:

• chr2-168532581-G-A
• chr2-168532581-G-C

Variant summary

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

The NM_203463.3(CERS6):​c.171-15015G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 151,748 control chromosomes in the GnomAD database, including 2,545 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 0.16 (2545 hom., cov: 32)
• Consequence: CERS6 NM_203463.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CERS6	NM_203463.3	c.171-15015G>A		intron_variant		ENST00000305747.11	NP_982288.1
CERS6	NM_001256126.2	c.171-15015G>A		intron_variant			NP_001243055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CERS6	ENST00000305747.11	c.171-15015G>A		intron_variant		2	NM_203463.3	ENSP00000306579.6
CERS6	ENST00000392687.4	c.171-15015G>A		intron_variant		1		ENSP00000376453.4

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24513 AN: 151630 Hom.: 2547 Cov.: 32

Gnomad AFR AF: 0.0461

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.0145

Gnomad SAS AF: 0.0892

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.162 AC: 24508 AN: 151748 Hom.: 2545 Cov.: 32 AF XY: 0.160 AC XY: 11892 AN XY: 74148

Gnomad4 AFR AF: 0.0460

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.0145

Gnomad4 SAS AF: 0.0891

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.182

Alfa AF: 0.205 Hom.: 7408

Bravo AF: 0.150

Asia WGS AF: 0.0560 AC: 196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.072
DANN	Benign	0.43

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: rs13393173; hg19: chr2-169389091;