12-50152342-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CERS5	NM_147190.5	c.198-8285C>A		intron_variant		ENST00000317551.12
LOC124902931	XR_007063304.1	n.492+8651G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CERS5	ENST00000317551.12	c.198-8285C>A		intron_variant		2	NM_147190.5	P1
	ENST00000548468.2	n.106-12684G>T		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.733

Gnomad4 ASJ AF: 0.755

Gnomad4 EAS AF: 0.838

Gnomad4 SAS AF: 0.607

Gnomad4 FIN AF: 0.723

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.673

Alfa AF: 0.604 Hom.: 2924

Bravo AF: 0.663

Asia WGS AF: 0.698 AC: 2424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.17
Dann	Benign	0.34

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: rs7972465; hg19: chr12-50546125;