2-168774325-G-T

Position:

• chr2-168774325-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_203463.3(CERS6):​c.*4663G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 152,190 control chromosomes in the GnomAD database, including 48,522 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 0.79 (48519 hom., cov: 32)
  • Exomes 𝑓: 0.88 (3 hom.)
• Consequence: CERS6 NM_203463.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.279

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]

CERS6-AS1 (HGNC:44485): (CERS6 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CERS6	NM_203463.3	c.*4663G>T		3_prime_UTR_variant	10/10	ENST00000305747.11	NP_982288.1
CERS6-AS1	NR_045787.1	n.518C>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CERS6	ENST00000305747.11	c.*4663G>T		3_prime_UTR_variant	10/10	2	NM_203463.3	ENSP00000306579	A1
CERS6-AS1	ENST00000425636.6	n.518C>A		non_coding_transcript_exon_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.794 AC: 120750 AN: 152066 Hom.: 48463 Cov.: 32

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.816

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.967

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.653

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.770

GnomAD4 exome AF: 0.875 AC: 7 AN: 8 Hom.: 3 Cov.: 0 AF XY: 0.875 AC XY: 7 AN XY: 8

Gnomad4 NFE exome AF: 0.875

GnomAD4 genome AF: 0.794 AC: 120864 AN: 152182 Hom.: 48519 Cov.: 32 AF XY: 0.799 AC XY: 59479 AN XY: 74406

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.816

Gnomad4 ASJ AF: 0.726

Gnomad4 EAS AF: 0.968

Gnomad4 SAS AF: 0.748

Gnomad4 FIN AF: 0.816

Gnomad4 NFE AF: 0.725

Gnomad4 OTH AF: 0.773

Alfa AF: 0.755 Hom.: 16808

Bravo AF: 0.801

Asia WGS AF: 0.840 AC: 2920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.8
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: rs8304; hg19: chr2-169630835;