dbSNP rs3747532: CER1:p.Ala65Gly (chr9-14722479-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005454.3(CER1):c.194C>G(p.Ala65Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 1,613,888 control chromosomes in the GnomAD database, including 101,211 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.43 ( 17446 hom., cov: 32)

Exomes 𝑓: 0.33 ( 83765 hom. )

Consequence

CER1
NM_005454.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.121

Publications

33 publications found

Variant links:

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]

CER1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_005454.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=1.5569218E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CER1	NM_005454.3	MANE Select	c.194C>G	p.Ala65Gly	missense	Exon 1 of 2	NP_005445.1	O95813

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CER1	ENST00000380911.4	TSL:1 MANE Select	c.194C>G	p.Ala65Gly	missense	Exon 1 of 2	ENSP00000370297.3	O95813

Frequencies

GnomAD3 genomes

AF:

0.433

AC:

65769

AN:

151938

Hom.:

17417

Cov.:

show subpopulations

Gnomad AFR

AF:

0.753

Gnomad AMI

AF:

0.180

Gnomad AMR

AF:

0.342

Gnomad ASJ

AF:

0.221

Gnomad EAS

AF:

0.0888

Gnomad SAS

AF:

0.315

Gnomad FIN

AF:

0.374

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.318

Gnomad OTH

AF:

0.392

GnomAD2 exomes

AF:

0.330

AC:

82875

AN:

251410

AF XY:

0.323

show subpopulations

Gnomad AFR exome

AF:

0.764

Gnomad AMR exome

AF:

0.309

Gnomad ASJ exome

AF:

0.229

Gnomad EAS exome

AF:

0.0923

Gnomad FIN exome

AF:

0.358

Gnomad NFE exome

AF:

0.317

Gnomad OTH exome

AF:

0.318

GnomAD4 exome

AF:

0.326

AC:

477165

AN:

1461832

Hom.:

83765

Cov.:

AF XY:

0.325

AC XY:

236009

AN XY:

727222

show subpopulations

African (AFR)

AF:

0.769

AC:

25759

AN:

33480

American (AMR)

AF:

0.311

AC:

13889

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.225

AC:

5891

AN:

26134

East Asian (EAS)

AF:

0.0689

AC:

2736

AN:

39700

South Asian (SAS)

AF:

0.332

AC:

28644

AN:

86258

European-Finnish (FIN)

AF:

0.355

AC:

18932

AN:

53396

Middle Eastern (MID)

AF:

0.294

AC:

1698

AN:

5766

European-Non Finnish (NFE)

AF:

0.323

AC:

359668

AN:

1111982

Other (OTH)

AF:

0.330

AC:

19948

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

19432

38865

58297

77730

97162

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11822

23644

35466

47288

59110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.433

AC:

65850

AN:

152056

Hom.:

17446

Cov.:

AF XY:

0.430

AC XY:

31990

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.752

AC:

31206

AN:

41474

American (AMR)

AF:

0.342

AC:

5222

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.221

AC:

767

AN:

3472

East Asian (EAS)

AF:

0.0884

AC:

457

AN:

5168

South Asian (SAS)

AF:

0.315

AC:

1516

AN:

4806

European-Finnish (FIN)

AF:

0.374

AC:

3950

AN:

10568

Middle Eastern (MID)

AF:

0.323

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.319

AC:

21653

AN:

67974

Other (OTH)

AF:

0.389

AC:

820

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1612

3224

4836

6448

8060

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

556

1112

1668

2224

2780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.295

Hom.:

5436

Bravo

AF:

0.441

Asia WGS

AF:

0.238

AC:

833

AN:

3478

EpiCase

AF:

0.311

EpiControl

AF:

0.307

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.8

(source)

DANN

Benign

0.40

DEOGEN2

Benign

0.083

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0040

LIST_S2

Benign

0.14

MetaRNN

Benign

0.0000016

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.3

PhyloP100

0.12

PrimateAI

Benign

0.37

PROVEAN

Benign

0.70

REVEL

Benign

0.053

Sift

Benign

1.0

Sift4G

Benign

1.0

PromoterAI

-0.0026

Neutral

(source)

Varity_R

0.023

gMVP

0.13

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over