rs1494359

Positions:

• chr9-14721768-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CER1	NM_005454.3	c.507+398T>C		intron_variant		ENST00000380911.4
CER1	XR_001746419.2	n.568+398T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CER1	ENST00000380911.4	c.507+398T>C		intron_variant		1	NM_005454.3	P1

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

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.0588

Gnomad4 ASJ AF: 0.0302

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0369

Gnomad4 FIN AF: 0.0296

Gnomad4 NFE AF: 0.0300

Gnomad4 OTH AF: 0.0766

Alfa AF: 0.0523 Hom.: 449

Bravo AF: 0.114

Asia WGS AF: 0.0340 AC: 119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.2
DANN	Benign	0.61

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: rs1494359; hg19: chr9-14721766;