12-50130181-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_147190.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERS5	NM_147190.5	MANE Select	c.*364A>G		3_prime_UTR	Exon 10 of 10	NP_671723.1	Q8N5B7-1
	CERS5	NM_001331070.3		c.*500A>G		3_prime_UTR	Exon 11 of 11	NP_001317999.1
	CERS5	NM_001331071.3		c.*500A>G		3_prime_UTR	Exon 11 of 11	NP_001318000.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERS5	ENST00000317551.12	TSL:2 MANE Select	c.*364A>G		3_prime_UTR	Exon 10 of 10	ENSP00000325485.6	Q8N5B7-1
	CERS5	ENST00000380189.8	TSL:1	n.*2004A>G		non_coding_transcript_exon	Exon 10 of 10	ENSP00000369536.4	Q49AQ3
	CERS5	ENST00000380189.8	TSL:1	n.*2004A>G		3_prime_UTR	Exon 10 of 10	ENSP00000369536.4	Q49AQ3

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

African (AFR) AF: 0.890 AC: 739 AN: 830

American (AMR) AF: 0.681 AC: 830 AN: 1218

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 460 AN: 894

East Asian (EAS) AF: 0.919 AC: 1163 AN: 1266

South Asian (SAS) AF: 0.751 AC: 536 AN: 714

European-Finnish (FIN) AF: 0.638 AC: 1000 AN: 1568

Middle Eastern (MID) AF: 0.545 AC: 61 AN: 112

European-Non Finnish (NFE) AF: 0.622 AC: 9828 AN: 15812

Other (OTH) AF: 0.651 AC: 1033 AN: 1586

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

African (AFR) AF: 0.882 AC: 36602 AN: 41500

American (AMR) AF: 0.680 AC: 10379 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1819 AN: 3468

East Asian (EAS) AF: 0.918 AC: 4747 AN: 5170

South Asian (SAS) AF: 0.778 AC: 3755 AN: 4826

European-Finnish (FIN) AF: 0.609 AC: 6429 AN: 10556

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.624 AC: 42376 AN: 67964

Other (OTH) AF: 0.682 AC: 1443 AN: 2116

Alfa AF: 0.642 Hom.: 55491

Bravo AF: 0.723

Asia WGS AF: 0.824 AC: 2864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.7
DANN	Benign	0.58
PhyloP100		0.68
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: rs7532; hg19: chr12-50523964;