2-168505032-C-T

Variant names:

• chr2-168505032-C-T
• rs12479292
• NM_203463.3:c.171-42564C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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 (EAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203463.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERS6	NM_203463.3	MANE Select	c.171-42564C>T		intron	N/A	NP_982288.1	Q6ZMG9-1
	CERS6	NM_001256126.2		c.171-42564C>T		intron	N/A	NP_001243055.1	Q6ZMG9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERS6	ENST00000305747.11	TSL:2 MANE Select	c.171-42564C>T		intron	N/A	ENSP00000306579.6	Q6ZMG9-1
	CERS6	ENST00000392687.4	TSL:1	c.171-42564C>T		intron	N/A	ENSP00000376453.4	Q6ZMG9-2
	CERS6	ENST00000947123.1		c.171-42564C>T		intron	N/A	ENSP00000617182.1

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

African (AFR) AF: 0.132 AC: 5466 AN: 41428

American (AMR) AF: 0.441 AC: 6728 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1878 AN: 3466

East Asian (EAS) AF: 0.641 AC: 3295 AN: 5140

South Asian (SAS) AF: 0.640 AC: 3074 AN: 4806

European-Finnish (FIN) AF: 0.438 AC: 4593 AN: 10482

Middle Eastern (MID) AF: 0.534 AC: 156 AN: 292

European-Non Finnish (NFE) AF: 0.436 AC: 29566 AN: 67888

Other (OTH) AF: 0.400 AC: 842 AN: 2104

Alfa AF: 0.423 Hom.: 60443

Bravo AF: 0.358

Asia WGS AF: 0.608 AC: 2116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.63
PhyloP100		-1.7
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: rs12479292; hg19: chr2-169361542;