rs1494359

Variant names:

• chr9-14721768-A-G
• rs1494359
• NM_005454.3:c.507+398T>C

Variant summary

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

The NM_005454.3(CER1):​c.507+398T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,188 control chromosomes in the GnomAD database, including 1,856 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 0.10 (1856 hom., cov: 32)
• Consequence: CER1 NM_005454.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.331
• Publications: 2 publications found

Genes affected

CER1 (HGNC:1862): (cerberus 1, DAN family BMP antagonist) This gene encodes a cytokine member of the cysteine knot superfamily, characterized by nine conserved cysteines and a cysteine knot region. The cerberus-related cytokines, together with Dan and DRM/Gremlin, represent a group of bone morphogenetic protein (BMP) antagonists that can bind directly to BMPs and inhibit their activity. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005454.3. 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
	CER1	NM_005454.3	MANE Select	c.507+398T>C		intron	N/A	NP_005445.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CER1	ENST00000380911.4	TSL:1 MANE Select	c.507+398T>C		intron	N/A	ENSP00000370297.3

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15777 AN: 152070 Hom.: 1851 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0589

Gnomad ASJ AF: 0.0302

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0379

Gnomad FIN AF: 0.0296

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0300

Gnomad OTH AF: 0.0779

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

GnomAD4 genome AF: 0.104 AC: 15803 AN: 152188 Hom.: 1856 Cov.: 32 AF XY: 0.102 AC XY: 7612 AN XY: 74426

African (AFR) AF: 0.291 AC: 12077 AN: 41476

American (AMR) AF: 0.0588 AC: 900 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0302 AC: 105 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.0369 AC: 178 AN: 4824

European-Finnish (FIN) AF: 0.0296 AC: 314 AN: 10614

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0300 AC: 2039 AN: 68010

Other (OTH) AF: 0.0766 AC: 162 AN: 2114

Alfa AF: 0.0551 Hom.: 548

Bravo AF: 0.114

Asia WGS AF: 0.0340 AC: 119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.2
DANN	Benign	0.61
PhyloP100		0.33
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: rs1494359; hg19: chr9-14721766;