rs1945085

Variant names:

• chr11-77026201-A-G
• rs1945085
• NM_018367.7:c.*5874A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

ACER3 Gene-Disease associations (from GenCC):

• alkaline ceramidase 3 deficiency

  Inheritance: Unknown, AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACER3-AS1 (HGNC:58067):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018367.7. 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
	ACER3	NM_018367.7	MANE Select	c.*5874A>G		3_prime_UTR	Exon 11 of 11	NP_060837.3
	ACER3	NM_001300953.2		c.*5874A>G		3_prime_UTR	Exon 10 of 10	NP_001287882.1
	ACER3	NM_001300954.2		c.*5874A>G		3_prime_UTR	Exon 11 of 11	NP_001287883.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACER3	ENST00000532485.6	TSL:1 MANE Select	c.*5874A>G		3_prime_UTR	Exon 11 of 11	ENSP00000434480.1
	ACER3-AS1	ENST00000804914.1		n.117+9367T>C		intron	N/A

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.500 AC: 1 AN: 2

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

African (AFR) AF: 0.118 AC: 4887 AN: 41508

American (AMR) AF: 0.356 AC: 5445 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1672 AN: 3464

East Asian (EAS) AF: 0.259 AC: 1340 AN: 5174

South Asian (SAS) AF: 0.456 AC: 2200 AN: 4822

European-Finnish (FIN) AF: 0.537 AC: 5662 AN: 10538

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.557 AC: 37841 AN: 67968

Other (OTH) AF: 0.400 AC: 843 AN: 2106

Alfa AF: 0.514 Hom.: 10779

Bravo AF: 0.371

Asia WGS AF: 0.350 AC: 1218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.3
DANN	Benign	0.59
PhyloP100		1.6
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: rs1945085; hg19: chr11-76737245;