Genetic Variant NM_001670.3:c.2872G>A (chr22-19971245-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001670.3(ARVCF):c.2872G>A(p.Val958Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000113 in 1,555,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

ARVCF
NM_001670.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 5.38

Publications

4 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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13378367).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001670.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARVCF	NM_001670.3	MANE Select	c.2872G>A	p.Val958Ile	missense	Exon 19 of 20	NP_001661.1	O00192-1
ARVCF	NM_001438684.1		c.2854G>A	p.Val952Ile	missense	Exon 18 of 18	NP_001425613.1
ARVCF	NM_001438685.1		c.2839G>A	p.Val947Ile	missense	Exon 18 of 19	NP_001425614.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARVCF	ENST00000263207.8	TSL:1 MANE Select	c.2872G>A	p.Val958Ile	missense	Exon 19 of 20	ENSP00000263207.3	O00192-1
ARVCF	ENST00000406259.1	TSL:5	c.2854G>A	p.Val952Ile	missense	Exon 16 of 16	ENSP00000385444.1	E9PDC3
ARVCF	ENST00000852538.1		c.2839G>A	p.Val947Ile	missense	Exon 18 of 19	ENSP00000522597.1

Frequencies

GnomAD3 genomes

AF:

0.0000985

AC:

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000234

AC:

AN:

162058

AF XY:

0.000211

show subpopulations

Gnomad AFR exome

AF:

0.000212

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000142

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000115

AC:

161

AN:

1402916

Hom.:

Cov.:

AF XY:

0.000120

AC XY:

AN XY:

692268

show subpopulations

African (AFR)

AF:

0.0000626

AC:

AN:

31940

American (AMR)

AF:

0.00

AC:

AN:

36292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25204

East Asian (EAS)

AF:

0.00

AC:

AN:

36278

South Asian (SAS)

AF:

0.000918

AC:

AN:

79538

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49170

Middle Eastern (MID)

AF:

0.00105

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.0000694

AC:

AN:

1080620

Other (OTH)

AF:

0.0000860

AC:

AN:

58168

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000984

AC:

AN:

152370

Hom.:

Cov.:

AF XY:

0.0000939

AC XY:

AN XY:

74518

show subpopulations

African (AFR)

AF:

0.0000240

AC:

AN:

41588

American (AMR)

AF:

0.000131

AC:

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68028

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000102

Hom.:

Bravo

AF:

0.0000907

ESP6500AA

AF:

0.000231

AC:

ESP6500EA

AF:

0.000588

AC:

ExAC

AF:

0.000145

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.010

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.98

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.64

MutationAssessor

Benign

1.6

PhyloP100

5.4

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.18

REVEL

Benign

0.16

Sift

Uncertain

0.011

Sift4G

Benign

0.13

Polyphen

0.98

Vest4

0.50

MVP

0.77

MPC

0.51

ClinPred

0.13

GERP RS

4.1

Varity_R

0.14

gMVP

0.12

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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