2-168774325-G-T

Variant names:

• chr2-168774325-G-T
• rs8304
• ENST00000425636.6:n.518C>A

Variant summary

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

The ENST00000425636.6(CERS6-AS1):​n.518C>A variant causes a non coding transcript exon 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-AS1 ENST00000425636.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.279
• Publications: 5 publications found

Genes affected

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

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=-0.89).
• 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 rank	MANE	Protein	UniProt
CERS6	NM_203463.3	c.*4663G>T		3_prime_UTR_variant	Exon 10 of 10	ENST00000305747.11	NP_982288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERS6	ENST00000305747.11	c.*4663G>T		3_prime_UTR_variant	Exon 10 of 10	2	NM_203463.3	ENSP00000306579.6

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.875 AC: 7 AN: 8

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.889 AC: 36914 AN: 41524

American (AMR) AF: 0.816 AC: 12473 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 2520 AN: 3472

East Asian (EAS) AF: 0.968 AC: 5013 AN: 5180

South Asian (SAS) AF: 0.748 AC: 3608 AN: 4824

European-Finnish (FIN) AF: 0.816 AC: 8648 AN: 10594

Middle Eastern (MID) AF: 0.661 AC: 193 AN: 292

European-Non Finnish (NFE) AF: 0.725 AC: 49270 AN: 67986

Other (OTH) AF: 0.773 AC: 1631 AN: 2110

Alfa AF: 0.761 Hom.: 27993

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
PhyloP100		0.28
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: rs8304; hg19: chr2-169630835;