rs7258249

Variant names:

• chr19-8206837-G-A
• rs7258249
• ENST00000561008.5:c.-191+38G>A

Variant summary

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

The ENST00000561008.5(CERS4):​c.-191+38G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 155,618 control chromosomes in the GnomAD database, including 12,144 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 0.37 (11852 hom., cov: 29)
  • Exomes 𝑓: 0.34 (292 hom.)
• Consequence: CERS4 ENST00000561008.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.259
• Publications: 31 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERS4	ENST00000561008.5	c.-191+38G>A		intron_variant	Intron 1 of 3	4		ENSP00000453796.1

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55822 AN: 151492 Hom.: 11848 Cov.: 29

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.0561

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.391

GnomAD4 exome AF: 0.344 AC: 1378 AN: 4008 Hom.: 292 Cov.: 0 AF XY: 0.343 AC XY: 713 AN XY: 2078

African (AFR) AF: 0.146 AC: 12 AN: 82

American (AMR) AF: 0.238 AC: 20 AN: 84

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 47 AN: 114

East Asian (EAS) AF: 0.0528 AC: 34 AN: 644

South Asian (SAS) AF: 0.339 AC: 19 AN: 56

European-Finnish (FIN) AF: 0.322 AC: 178 AN: 552

Middle Eastern (MID) AF: 0.300 AC: 3 AN: 10

European-Non Finnish (NFE) AF: 0.432 AC: 976 AN: 2258

Other (OTH) AF: 0.428 AC: 89 AN: 208

GnomAD4 genome AF: 0.368 AC: 55845 AN: 151610 Hom.: 11852 Cov.: 29 AF XY: 0.361 AC XY: 26757 AN XY: 74028

African (AFR) AF: 0.198 AC: 8196 AN: 41362

American (AMR) AF: 0.319 AC: 4831 AN: 15150

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1813 AN: 3466

East Asian (EAS) AF: 0.0561 AC: 289 AN: 5154

South Asian (SAS) AF: 0.346 AC: 1663 AN: 4804

European-Finnish (FIN) AF: 0.387 AC: 4063 AN: 10488

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33552 AN: 67876

Other (OTH) AF: 0.386 AC: 812 AN: 2106

Alfa AF: 0.451 Hom.: 44598

Bravo AF: 0.356

Asia WGS AF: 0.184 AC: 642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.59
PhyloP100		0.26
PromoterAI		-0.037	Neutral

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: rs7258249; hg19: chr19-8271721;