rs1945085

Positions:

• chr11-77026201-A-G
• chr11-77026201-A-T

Variant summary

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

The NM_018367.7(ACER3):​c.*5874A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,062 control chromosomes in the GnomAD database, including 14,750 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 0.40 (14750 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: ACER3 NM_018367.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57

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]

LOC124902721 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACER3	NM_018367.7	c.*5874A>G		3_prime_UTR_variant	11/11	ENST00000532485.6	NP_060837.3
LOC124902721	XR_007062792.1	n.117+9367T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACER3	ENST00000532485.6	c.*5874A>G		3_prime_UTR_variant	11/11	1	NM_018367.7	ENSP00000434480	P1

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60413 AN: 151940 Hom.: 14747 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.398

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.397 AC: 60420 AN: 152060 Hom.: 14750 Cov.: 32 AF XY: 0.393 AC XY: 29202 AN XY: 74328

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.400

Alfa AF: 0.516 Hom.: 9645

Bravo AF: 0.371

Asia WGS AF: 0.350 AC: 1218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.3
DANN	Benign	0.59

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: rs1945085; hg19: chr11-76737245;