12-50130181-T-C

Variant names:

• chr12-50130181-T-C
• rs7532
• NM_147190.5:c.*364A>G

Variant summary

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

The NM_147190.5(CERS5):​c.*364A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 176,074 control chromosomes in the GnomAD database, including 45,023 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 0.71 (39775 hom., cov: 31)
  • Exomes 𝑓: 0.65 (5248 hom.)
• Consequence: CERS5 NM_147190.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.682

Genes affected

CERS5 (HGNC:23749): (ceramide synthase 5) This gene encodes a protein that belongs to the TLC (TRAM, LAG1 and CLN8 homology domains) family of proteins. The encoded protein functions in the synthesis of ceramide, a lipid molecule that is involved in a several cellular signaling pathways. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ENSG00000272368 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERS5	NM_147190.5	c.*364A>G		3_prime_UTR_variant	Exon 10 of 10	ENST00000317551.12	NP_671723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERS5	ENST00000317551	c.*364A>G		3_prime_UTR_variant	Exon 10 of 10	2	NM_147190.5	ENSP00000325485.6

Frequencies

GnomAD3 genomes AF: 0.712 AC: 108132 AN: 151956 Hom.: 39725 Cov.: 31

Gnomad AFR AF: 0.882

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.918

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.682

GnomAD4 exome AF: 0.652 AC: 15650 AN: 24000 Hom.: 5248 Cov.: 0 AF XY: 0.647 AC XY: 8031 AN XY: 12420

Gnomad4 AFR exome AF: 0.890

Gnomad4 AMR exome AF: 0.681

Gnomad4 ASJ exome AF: 0.515

Gnomad4 EAS exome AF: 0.919

Gnomad4 SAS exome AF: 0.751

Gnomad4 FIN exome AF: 0.638

Gnomad4 NFE exome AF: 0.622

Gnomad4 OTH exome AF: 0.651

GnomAD4 genome AF: 0.712 AC: 108236 AN: 152074 Hom.: 39775 Cov.: 31 AF XY: 0.712 AC XY: 52928 AN XY: 74338

Gnomad4 AFR AF: 0.882

Gnomad4 AMR AF: 0.680

Gnomad4 ASJ AF: 0.525

Gnomad4 EAS AF: 0.918

Gnomad4 SAS AF: 0.778

Gnomad4 FIN AF: 0.609

Gnomad4 NFE AF: 0.624

Gnomad4 OTH AF: 0.682

Alfa AF: 0.633 Hom.: 39499

Bravo AF: 0.723

Asia WGS AF: 0.824 AC: 2864 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	6.7
DANN	Benign	0.58

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: rs7532; hg19: chr12-50523964;