2-168706525-A-G

Position:

• chr2-168706525-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.87).
• 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/exons	MANE	Protein	UniProt
CERS6	NM_203463.3	c.610-8476A>G		intron_variant		ENST00000305747.11	NP_982288.1
CERS6	NM_001256126.2	c.610-8476A>G		intron_variant			NP_001243055.1
CERS6	XM_005246440.6	c.34-8476A>G		intron_variant			XP_005246497.1
CERS6	XM_017003749.3	c.187-8476A>G		intron_variant			XP_016859238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CERS6	ENST00000305747.11	c.610-8476A>G		intron_variant		2	NM_203463.3	ENSP00000306579	A1
CERS6	ENST00000392687.4	c.610-8476A>G		intron_variant		1		ENSP00000376453	P4

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

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.0468

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00787

Gnomad4 FIN AF: 0.0637

Gnomad4 NFE AF: 0.0491

Gnomad4 OTH AF: 0.0573

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

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: rs10490709; hg19: chr2-169563035;