chr2-168674036-G-A

Variant names:

• chr2-168674036-G-A
• rs10930335
• NM_203463.3:c.466-16998G>A

Variant summary

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

The NM_203463.3(CERS6):​c.466-16998G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.915 in 152,192 control chromosomes in the GnomAD database, including 63,756 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 0.92 (63756 hom., cov: 31)
• Consequence: CERS6 NM_203463.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0200
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.952 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.466-16998G>A		intron	N/A	NP_982288.1	Q6ZMG9-1
	CERS6	NM_001256126.2		c.466-16998G>A		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.466-16998G>A		intron	N/A	ENSP00000306579.6	Q6ZMG9-1
	CERS6	ENST00000392687.4	TSL:1	c.466-16998G>A		intron	N/A	ENSP00000376453.4	Q6ZMG9-2
	CERS6	ENST00000947123.1		c.466-11287G>A		intron	N/A	ENSP00000617182.1

Frequencies

GnomAD3 genomes AF: 0.915 AC: 139161 AN: 152074 Hom.: 63702 Cov.: 31

Gnomad AFR AF: 0.925

Gnomad AMI AF: 0.865

Gnomad AMR AF: 0.937

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.975

Gnomad SAS AF: 0.866

Gnomad FIN AF: 0.910

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.908

Gnomad OTH AF: 0.892

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

GnomAD4 genome AF: 0.915 AC: 139271 AN: 152192 Hom.: 63756 Cov.: 31 AF XY: 0.914 AC XY: 68029 AN XY: 74400

African (AFR) AF: 0.925 AC: 38408 AN: 41512

American (AMR) AF: 0.938 AC: 14329 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.856 AC: 2972 AN: 3472

East Asian (EAS) AF: 0.975 AC: 5043 AN: 5174

South Asian (SAS) AF: 0.865 AC: 4169 AN: 4820

European-Finnish (FIN) AF: 0.910 AC: 9637 AN: 10594

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.908 AC: 61787 AN: 68022

Other (OTH) AF: 0.893 AC: 1886 AN: 2112

Alfa AF: 0.910 Hom.: 114323

Bravo AF: 0.920

Asia WGS AF: 0.921 AC: 3205 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	9.5
DANN	Benign	0.78
PhyloP100		-0.020
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: rs10930335; hg19: chr2-169530546;