rs10115703

chr9-14722618-G-Achr9-14722618-G-Cchr9-14722618-G-T

Variant summary

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

The NM_005454.3(CER1):c.55C>T(p.Arg19Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0866 in 1,607,698 control chromosomes in the GnomAD database, including 6,865 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.093 (711 hom., cov: 32)
  • Exomes 𝑓: 0.086 (6154 hom.)
• Consequence: CER1 NM_005454.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19

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 (MetaRNN=0.0010258853).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CER1	NM_005454.3	c.55C>T	p.Arg19Trp	missense_variant	1/2	ENST00000380911.4
CER1	XR_001746419.2	n.116C>T		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CER1	ENST00000380911.4	c.55C>T	p.Arg19Trp	missense_variant	1/2	1	NM_005454.3	P1

Frequencies

GnomAD3 genomes AF: 0.0927 AC: 14105 AN: 152098 Hom.: 707 Cov.: 32

Gnomad AFR AF: 0.0982

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0559

Gnomad EAS AF: 0.00925

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0797

Gnomad OTH AF: 0.0900

GnomAD3 exomes AF: 0.101 AC: 24966 AN: 246786 Hom.: 1607 AF XY: 0.101 AC XY: 13486 AN XY: 133748

Gnomad AFR exome AF: 0.0953

Gnomad AMR exome AF: 0.184

Gnomad ASJ exome AF: 0.0518

Gnomad EAS exome AF: 0.00870

Gnomad SAS exome AF: 0.143

Gnomad FIN exome AF: 0.119

Gnomad NFE exome AF: 0.0827

Gnomad OTH exome AF: 0.0943

GnomAD4 exome AF: 0.0859 AC: 125097 AN: 1455482 Hom.: 6154 Cov.: 33 AF XY: 0.0874 AC XY: 63296 AN XY: 724308

Gnomad4 AFR exome AF: 0.0974

Gnomad4 AMR exome AF: 0.175

Gnomad4 ASJ exome AF: 0.0513

Gnomad4 EAS exome AF: 0.00587

Gnomad4 SAS exome AF: 0.142

Gnomad4 FIN exome AF: 0.115

Gnomad4 NFE exome AF: 0.0804

Gnomad4 OTH exome AF: 0.0791

GnomAD4 genome AF: 0.0928 AC: 14133 AN: 152216 Hom.: 711 Cov.: 32 AF XY: 0.0961 AC XY: 7155 AN XY: 74418

Gnomad4 AFR AF: 0.0982

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.0559

Gnomad4 EAS AF: 0.00927

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.0797

Gnomad4 OTH AF: 0.0900

Alfa AF: 0.0784 Hom.: 1217

Bravo AF: 0.0928

TwinsUK AF: 0.0863 AC: 320

ALSPAC AF: 0.0768 AC: 296

ESP6500AA AF: 0.0949 AC: 418

ESP6500EA AF: 0.0829 AC: 713

ExAC AF: 0.0995 AC: 12078

Asia WGS AF: 0.0870 AC: 303 AN: 3478

EpiCase AF: 0.0785

EpiControl AF: 0.0797

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.030
Dann	Benign	0.44
DEOGEN2	Benign	0.082	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.45	T
MetaRNN	Benign	0.0010	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.095	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.062
Sift	Benign	0.046	D
Sift4G	Uncertain	0.027	D
Polyphen		0.0020	B
Vest4		0.045
MPC		0.0066
ClinPred		0.011	T
GERP RS		-12
Varity_R		0.035
gMVP		0.27

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: rs10115703; hg19: chr9-14722616; COSMIC: COSV66603069;