rs2967625

Positions:

• chr19-8233527-G-A
• chr19-8233527-G-C
• chr19-8233527-G-T

Variant summary

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

The NM_024552.3(CERS4):​c.-1-17549G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 151,560 control chromosomes in the GnomAD database, including 15,990 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 0.46 (15990 hom., cov: 29)
• Consequence: CERS4 NM_024552.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118

Genes affected

CERS4 (HGNC:23747): (ceramide synthase 4) Enables sphingosine N-acyltransferase activity. Involved in ceramide biosynthetic process. Predicted to be located in endoplasmic reticulum membrane. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CERS4	NM_024552.3	c.-1-17549G>A		intron_variant		ENST00000251363.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CERS4	ENST00000251363.10	c.-1-17549G>A		intron_variant		1	NM_024552.3	P1
	ENST00000605980.1	n.291+5831C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69220 AN: 151442 Hom.: 15983 Cov.: 29

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.457 AC: 69264 AN: 151560 Hom.: 15990 Cov.: 29 AF XY: 0.457 AC XY: 33800 AN XY: 74024

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.474

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.528

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.477

Alfa AF: 0.474 Hom.: 35632

Bravo AF: 0.454

Asia WGS AF: 0.391 AC: 1360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.3
DANN	Benign	0.82

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: rs2967625; hg19: chr19-8298411;