22-19971950-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001670.3(ARVCF):c.2717G>A(p.Arg906Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 1,611,770 control chromosomes in the GnomAD database, including 539,767 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 41422 hom., cov: 35)

Exomes 𝑓: 0.82 ( 498345 hom. )

Consequence

ARVCF
NM_001670.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.89

Publications

67 publications found

Variant links:

Genes affected

ARVCF (HGNC:728): (ARVCF delta catenin family member) Armadillo Repeat gene deleted in Velo-Cardio-Facial syndrome (ARVCF) is a member of the catenin family. This family plays an important role in the formation of adherens junction complexes, which are thought to facilitate communication between the inside and outside environments of a cell. The ARVCF gene was isolated in the search for the genetic defect responsible for the autosomal dominant Velo-Cardio-Facial syndrome (VCFS), a relatively common human disorder with phenotypic features including cleft palate, conotruncal heart defects and facial dysmorphology. The ARVCF gene encodes a protein containing two motifs, a coiled coil domain in the N-terminus and a 10 armadillo repeat sequence in the midregion. Since these sequences can facilitate protein-protein interactions ARVCF is thought to function in a protein complex. In addition, ARVCF contains a predicted nuclear-targeting sequence suggesting that it may have a function as a nuclear protein. [provided by RefSeq, Jun 2010]

ARVCF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.458212E-7).

BP6

Variant 22-19971950-C-T is Benign according to our data. Variant chr22-19971950-C-T is described in ClinVar as Benign. ClinVar VariationId is 1234835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARVCF	NM_001670.3 link	c.2717G>A	p.Arg906Gln	missense_variant	Exon 18 of 20	ENST00000263207.8	NP_001661.1	O00192-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARVCF	ENST00000263207.8 link	c.2717G>A	p.Arg906Gln	missense_variant	Exon 18 of 20	1	NM_001670.3	ENSP00000263207.3		O00192-1

Frequencies

GnomAD3 genomes

AF:

0.720

AC:

109508

AN:

152096

Hom.:

41420

Cov.:

show subpopulations

Gnomad AFR

AF:

0.499

Gnomad AMI

AF:

0.909

Gnomad AMR

AF:

0.675

Gnomad ASJ

AF:

0.847

Gnomad EAS

AF:

0.503

Gnomad SAS

AF:

0.726

Gnomad FIN

AF:

0.794

Gnomad MID

AF:

0.873

Gnomad NFE

AF:

0.859

Gnomad OTH

AF:

0.743

GnomAD2 exomes

AF:

0.746

AC:

186140

AN:

249458

AF XY:

0.759

show subpopulations

Gnomad AFR exome

AF:

0.490

Gnomad AMR exome

AF:

0.583

Gnomad ASJ exome

AF:

0.838

Gnomad EAS exome

AF:

0.503

Gnomad FIN exome

AF:

0.798

Gnomad NFE exome

AF:

0.860

Gnomad OTH exome

AF:

0.792

GnomAD4 exome

AF:

0.821

AC:

1197590

AN:

1459556

Hom.:

498345

Cov.:

AF XY:

0.820

AC XY:

595343

AN XY:

726122

show subpopulations

African (AFR)

AF:

0.484

AC:

16212

AN:

33470

American (AMR)

AF:

0.591

AC:

26370

AN:

44606

Ashkenazi Jewish (ASJ)

AF:

0.836

AC:

21728

AN:

25988

East Asian (EAS)

AF:

0.522

AC:

20703

AN:

39686

South Asian (SAS)

AF:

0.724

AC:

62409

AN:

86174

European-Finnish (FIN)

AF:

0.805

AC:

42137

AN:

52342

Middle Eastern (MID)

AF:

0.818

AC:

4708

AN:

5758

European-Non Finnish (NFE)

AF:

0.860

AC:

955658

AN:

1111228

Other (OTH)

AF:

0.790

AC:

47665

AN:

60304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

10397

20795

31192

41590

51987

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21020

42040

63060

84080

105100

<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:

0.720

AC:

109525

AN:

152214

Hom.:

41422

Cov.:

AF XY:

0.715

AC XY:

53186

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.498

AC:

20691

AN:

41518

American (AMR)

AF:

0.674

AC:

10315

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.847

AC:

2939

AN:

3470

East Asian (EAS)

AF:

0.503

AC:

2601

AN:

5172

South Asian (SAS)

AF:

0.725

AC:

3498

AN:

4828

European-Finnish (FIN)

AF:

0.794

AC:

8422

AN:

10612

Middle Eastern (MID)

AF:

0.867

AC:

255

AN:

294

European-Non Finnish (NFE)

AF:

0.859

AC:

58410

AN:

67994

Other (OTH)

AF:

0.742

AC:

1565

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1420

2841

4261

5682

7102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

826

1652

2478

3304

4130

<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:

0.810

Hom.:

205305

Bravo

AF:

0.698

TwinsUK

AF:

0.856

AC:

3173

ALSPAC

AF:

0.857

AC:

3303

ESP6500AA

AF:

0.498

AC:

2193

ESP6500EA

AF:

0.857

AC:

7367

ExAC

AF:

0.750

AC:

90979

Asia WGS

AF:

0.613

AC:

2132

AN:

3478

EpiCase

AF:

0.855

EpiControl

AF:

0.858

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 20333729, 15861775) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.0064

T;.;T;.

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.59

T;T;T;T

MetaRNN

Benign

8.5e-7

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.84

L;.;.;.

PhyloP100

1.9

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.090

N;N;N;N

REVEL

Benign

0.088

Sift

Benign

0.54

T;T;T;T

Sift4G

Benign

0.83

T;T;T;T

Polyphen

0.0020

B;.;.;.

Vest4

0.074

MPC

0.14

ClinPred

0.0098

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.022

gMVP

0.14

Mutation Taster

=100/0

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over