11-76926686-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018367.7(ACER3):c.214+19C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 1,451,712 control chromosomes in the GnomAD database, including 345,519 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.57 (27907 hom., cov: 31)
  • Exomes 𝑓: 0.69 (317612 hom.)
• Consequence: ACER3 NM_018367.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0550

Genes affected

ACER3 (HGNC:16066): (alkaline ceramidase 3) Enables N-acylsphingosine amidohydrolase activity and metal ion binding activity. Involved in several processes, including myelination; positive regulation of cell population proliferation; and sphingolipid metabolic process. Is integral component of Golgi membrane and integral component of endoplasmic reticulum membrane. Biomarker of hepatocellular carcinoma and non-alcoholic steatohepatitis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-76926686-C-G is Benign according to our data. Variant chr11-76926686-C-G is described in ClinVar as [Benign]. Clinvar id is 1170184.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACER3	NM_018367.7	c.214+19C>G		intron_variant		ENST00000532485.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACER3	ENST00000532485.6	c.214+19C>G		intron_variant		1	NM_018367.7	P1

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86323 AN: 151854 Hom.: 27908 Cov.: 31

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.762

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.580

GnomAD3 exomes AF: 0.627 AC: 144082 AN: 229692 Hom.: 48085 AF XY: 0.643 AC XY: 80048 AN XY: 124456

Gnomad AFR exome AF: 0.227

Gnomad AMR exome AF: 0.417

Gnomad ASJ exome AF: 0.723

Gnomad EAS exome AF: 0.611

Gnomad SAS exome AF: 0.613

Gnomad FIN exome AF: 0.708

Gnomad NFE exome AF: 0.726

Gnomad OTH exome AF: 0.645

GnomAD4 exome AF: 0.691 AC: 898638 AN: 1299742 Hom.: 317612 Cov.: 19 AF XY: 0.694 AC XY: 453119 AN XY: 653274

Gnomad4 AFR exome AF: 0.210

Gnomad4 AMR exome AF: 0.432

Gnomad4 ASJ exome AF: 0.724

Gnomad4 EAS exome AF: 0.632

Gnomad4 SAS exome AF: 0.622

Gnomad4 FIN exome AF: 0.709

Gnomad4 NFE exome AF: 0.725

Gnomad4 OTH exome AF: 0.662

GnomAD4 genome AF: 0.568 AC: 86332 AN: 151970 Hom.: 27907 Cov.: 31 AF XY: 0.565 AC XY: 41958 AN XY: 74258

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.721

Gnomad4 EAS AF: 0.614

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.712

Gnomad4 NFE AF: 0.737

Gnomad4 OTH AF: 0.583

Alfa AF: 0.614 Hom.: 4079

Bravo AF: 0.543

Asia WGS AF: 0.559 AC: 1943 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.2
Dann	Benign	0.47

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: rs4604914; hg19: chr11-76637730;