22-19971950-C-T

Position:

chr22-19971950-C-T

Variant summary

Our verdict is Benign. Variant got -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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 made for transcript

Verdict is Benign. Variant got -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 id is 1234835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-19971950-C-T is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
ARVCF	NM_001670.3 linkuse as main transcript	c.2717G>A	p.Arg906Gln	missense_variant	18/20	ENST00000263207.8	NP_001661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARVCF	ENST00000263207.8 linkuse as main transcript	c.2717G>A	p.Arg906Gln	missense_variant	18/20	1	NM_001670.3	ENSP00000263207	P4	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

GnomAD3 exomes

AF:

0.746

AC:

186140

AN:

249458

Hom.:

72019

AF XY:

0.759

AC XY:

102355

AN XY:

134934

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 SAS exome

AF:

0.718

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

Gnomad4 AFR exome

AF:

0.484

Gnomad4 AMR exome

AF:

0.591

Gnomad4 ASJ exome

AF:

0.836

Gnomad4 EAS exome

AF:

0.522

Gnomad4 SAS exome

AF:

0.724

Gnomad4 FIN exome

AF:

0.805

Gnomad4 NFE exome

AF:

0.860

Gnomad4 OTH exome

AF:

0.790

GnomAD4 genome

AF:

0.720

AC:

109525

AN:

152214

Hom.:

41422

Cov.:

AF XY:

0.715

AC XY:

53186

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.498

Gnomad4 AMR

AF:

0.674

Gnomad4 ASJ

AF:

0.847

Gnomad4 EAS

AF:

0.503

Gnomad4 SAS

AF:

0.725

Gnomad4 FIN

AF:

0.794

Gnomad4 NFE

AF:

0.859

Gnomad4 OTH

AF:

0.742

Alfa

AF:

0.826

Hom.:

99229

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	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

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;.;.;.

MutationTaster

Benign

0.55

P;P;P;P;P

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over