12-50145636-T-G

Variant names:

• chr12-50145636-T-G
• rs7138945
• NM_147190.5:c.198-1579A>C

Variant summary

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

The NM_147190.5(CERS5):​c.198-1579A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 151,846 control chromosomes in the GnomAD database, including 9,194 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 0.34 (9194 hom., cov: 31)
• Consequence: CERS5 NM_147190.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.576
• Publications: 23 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERS5	NM_147190.5	c.198-1579A>C		intron_variant	Intron 1 of 9	ENST00000317551.12	NP_671723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERS5	ENST00000317551.12	c.198-1579A>C		intron_variant	Intron 1 of 9	2	NM_147190.5	ENSP00000325485.6

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52063 AN: 151730 Hom.: 9195 Cov.: 31

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.343 AC: 52083 AN: 151846 Hom.: 9194 Cov.: 31 AF XY: 0.335 AC XY: 24868 AN XY: 74192

African (AFR) AF: 0.378 AC: 15648 AN: 41360

American (AMR) AF: 0.272 AC: 4156 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 906 AN: 3466

East Asian (EAS) AF: 0.174 AC: 901 AN: 5184

South Asian (SAS) AF: 0.400 AC: 1927 AN: 4812

European-Finnish (FIN) AF: 0.282 AC: 2965 AN: 10498

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.361 AC: 24531 AN: 67960

Other (OTH) AF: 0.332 AC: 699 AN: 2108

Alfa AF: 0.345 Hom.: 14127

Bravo AF: 0.342

Asia WGS AF: 0.317 AC: 1106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.5
DANN	Benign	0.49
PhyloP100		0.58
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: rs7138945; hg19: chr12-50539419;