2-168709674-G-A

Variant names:

• chr2-168709674-G-A
• rs1424937
• NM_203463.3:c.610-5327G>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.610-5327G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,030 control chromosomes in the GnomAD database, including 10,843 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 0.36 (10843 hom., cov: 32)
• Consequence: CERS6 NM_203463.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERS6	NM_203463.3	c.610-5327G>A		intron_variant	Intron 6 of 9	ENST00000305747.11	NP_982288.1
CERS6	NM_001256126.2	c.610-5327G>A		intron_variant	Intron 6 of 10		NP_001243055.1
CERS6	XM_017003749.3	c.187-5327G>A		intron_variant	Intron 3 of 7		XP_016859238.1
CERS6	XM_005246440.6	c.34-5327G>A		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.610-5327G>A		intron_variant	Intron 6 of 9	2	NM_203463.3	ENSP00000306579.6
CERS6	ENST00000392687.4	c.610-5327G>A		intron_variant	Intron 6 of 10	1		ENSP00000376453.4

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54227 AN: 151912 Hom.: 10849 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.357 AC: 54210 AN: 152030 Hom.: 10843 Cov.: 32 AF XY: 0.360 AC XY: 26721 AN XY: 74302

African (AFR) AF: 0.187 AC: 7780 AN: 41500

American (AMR) AF: 0.303 AC: 4627 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1330 AN: 3468

East Asian (EAS) AF: 0.220 AC: 1141 AN: 5186

South Asian (SAS) AF: 0.438 AC: 2108 AN: 4810

European-Finnish (FIN) AF: 0.504 AC: 5320 AN: 10558

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.452 AC: 30687 AN: 67922

Other (OTH) AF: 0.348 AC: 733 AN: 2106

Alfa AF: 0.414 Hom.: 52902

Bravo AF: 0.330

Asia WGS AF: 0.319 AC: 1111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.7
DANN	Benign	0.55
PhyloP100		0.085
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: rs1424937; hg19: chr2-169566184;