rs10490709

Variant names:

• chr2-168706525-A-G
• rs10490709
• NM_203463.3:c.610-8476A>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.610-8476A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0718 in 152,312 control chromosomes in the GnomAD database, including 572 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 0.072 (572 hom., cov: 33)
• Consequence: CERS6 NM_203463.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155
• Publications: 0 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERS6	NM_203463.3	c.610-8476A>G		intron_variant	Intron 6 of 9	ENST00000305747.11	NP_982288.1
CERS6	NM_001256126.2	c.610-8476A>G		intron_variant	Intron 6 of 10		NP_001243055.1
CERS6	XM_017003749.3	c.187-8476A>G		intron_variant	Intron 3 of 7		XP_016859238.1
CERS6	XM_005246440.6	c.34-8476A>G		intron_variant	Intron 3 of 7		XP_005246497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERS6	ENST00000305747.11	c.610-8476A>G		intron_variant	Intron 6 of 9	2	NM_203463.3	ENSP00000306579.6
CERS6	ENST00000392687.4	c.610-8476A>G		intron_variant	Intron 6 of 10	1		ENSP00000376453.4

Frequencies

GnomAD3 genomes AF: 0.0717 AC: 10913 AN: 152194 Hom.: 570 Cov.: 33

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0469

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00787

Gnomad FIN AF: 0.0637

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0491

Gnomad OTH AF: 0.0579

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

GnomAD4 genome AF: 0.0718 AC: 10937 AN: 152312 Hom.: 572 Cov.: 33 AF XY: 0.0699 AC XY: 5210 AN XY: 74482

African (AFR) AF: 0.144 AC: 5977 AN: 41558

American (AMR) AF: 0.0468 AC: 716 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00787 AC: 38 AN: 4826

European-Finnish (FIN) AF: 0.0637 AC: 676 AN: 10616

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0491 AC: 3338 AN: 68028

Other (OTH) AF: 0.0573 AC: 121 AN: 2112

Alfa AF: 0.0607 Hom.: 72

Bravo AF: 0.0730

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.37
DANN	Benign	0.51
PhyloP100		-0.15
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: rs10490709; hg19: chr2-169563035;