chr19-8220723-G-A

Variant names:

• chr19-8220723-G-A
• rs11666866
• NM_024552.3:c.-2+9861G>A

Variant summary

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

The NM_024552.3(CERS4):​c.-2+9861G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,046 control chromosomes in the GnomAD database, including 10,291 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 0.36 (10291 hom., cov: 32)
• Consequence: CERS4 NM_024552.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.881
• Publications: 12 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 = 0.414 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024552.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERS4	NM_024552.3	MANE Select	c.-2+9861G>A		intron	N/A	NP_078828.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERS4	ENST00000251363.10	TSL:1 MANE Select	c.-2+9861G>A		intron	N/A	ENSP00000251363.5
	CERS4	ENST00000559336.5	TSL:1	c.-2+9861G>A		intron	N/A	ENSP00000453815.1
	CERS4	ENST00000595722.5	TSL:1	n.385+6242G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54359 AN: 151938 Hom.: 10284 Cov.: 32

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.0534

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.358 AC: 54402 AN: 152046 Hom.: 10291 Cov.: 32 AF XY: 0.349 AC XY: 25942 AN XY: 74296

African (AFR) AF: 0.338 AC: 14013 AN: 41476

American (AMR) AF: 0.304 AC: 4646 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1357 AN: 3470

East Asian (EAS) AF: 0.0535 AC: 277 AN: 5180

South Asian (SAS) AF: 0.293 AC: 1412 AN: 4822

European-Finnish (FIN) AF: 0.294 AC: 3104 AN: 10550

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28411 AN: 67968

Other (OTH) AF: 0.370 AC: 779 AN: 2108

Alfa AF: 0.398 Hom.: 52838

Bravo AF: 0.358

Asia WGS AF: 0.167 AC: 582 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.6
DANN	Benign	0.77
PhyloP100		0.88
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: rs11666866; hg19: chr19-8285607;