NM_147190.5:c.198-8285C>A

Variant names:

• chr12-50152342-G-T
• rs7972465
• NM_147190.5:c.198-8285C>A

Variant summary

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

The NM_147190.5(CERS5):​c.198-8285C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 152,120 control chromosomes in the GnomAD database, including 33,582 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 0.66 (33582 hom., cov: 33)
• Consequence: CERS5 NM_147190.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.724
• Publications: 9 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=-1.06).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.817 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.198-8285C>A		intron	N/A	NP_671723.1	Q8N5B7-1
	CERS5	NM_001331070.3		c.198-8285C>A		intron	N/A	NP_001317999.1
	CERS5	NM_001331071.3		c.198-8285C>A		intron	N/A	NP_001318000.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERS5	ENST00000317551.12	TSL:2 MANE Select	c.198-8285C>A		intron	N/A	ENSP00000325485.6	Q8N5B7-1
	CERS5	ENST00000380189.8	TSL:1	n.198-8285C>A		intron	N/A	ENSP00000369536.4	Q49AQ3
	CERS5	ENST00000898651.1		c.198-8285C>A		intron	N/A	ENSP00000568710.1

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100577 AN: 152002 Hom.: 33539 Cov.: 33

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.674

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

GnomAD4 genome AF: 0.662 AC: 100681 AN: 152120 Hom.: 33582 Cov.: 33 AF XY: 0.670 AC XY: 49829 AN XY: 74354

African (AFR) AF: 0.624 AC: 25896 AN: 41494

American (AMR) AF: 0.733 AC: 11194 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2619 AN: 3470

East Asian (EAS) AF: 0.838 AC: 4348 AN: 5188

South Asian (SAS) AF: 0.607 AC: 2924 AN: 4816

European-Finnish (FIN) AF: 0.723 AC: 7643 AN: 10578

Middle Eastern (MID) AF: 0.613 AC: 179 AN: 292

European-Non Finnish (NFE) AF: 0.644 AC: 43778 AN: 67980

Other (OTH) AF: 0.673 AC: 1422 AN: 2114

Alfa AF: 0.606 Hom.: 3094

Bravo AF: 0.663

Asia WGS AF: 0.698 AC: 2424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.17
DANN	Benign	0.34
PhyloP100		-0.72
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: rs7972465; hg19: chr12-50546125;