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GeneBe

22-19971306-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001670.3(ARVCF):c.2811C>T(p.Pro937=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0556 in 1,555,452 control chromosomes in the GnomAD database, including 2,960 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.075 ( 535 hom., cov: 34)
Exomes 𝑓: 0.054 ( 2425 hom. )

Consequence

ARVCF
NM_001670.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.23
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 22-19971306-G-A is Benign according to our data. Variant chr22-19971306-G-A is described in ClinVar as [Benign]. Clinvar id is 1242019.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.23 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ARVCFNM_001670.3 linkuse as main transcriptc.2811C>T p.Pro937= synonymous_variant 19/20 ENST00000263207.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ARVCFENST00000263207.8 linkuse as main transcriptc.2811C>T p.Pro937= synonymous_variant 19/201 NM_001670.3 P4O00192-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0747
AC:
11369
AN:
152180
Hom.:
529
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.135
Gnomad AMI
AF:
0.0877
Gnomad AMR
AF:
0.0766
Gnomad ASJ
AF:
0.0844
Gnomad EAS
AF:
0.0319
Gnomad SAS
AF:
0.0894
Gnomad FIN
AF:
0.0236
Gnomad MID
AF:
0.0538
Gnomad NFE
AF:
0.0467
Gnomad OTH
AF:
0.0827
GnomAD3 exomes
AF:
0.0666
AC:
10683
AN:
160408
Hom.:
446
AF XY:
0.0688
AC XY:
5844
AN XY:
85002
show subpopulations
Gnomad AFR exome
AF:
0.144
Gnomad AMR exome
AF:
0.0714
Gnomad ASJ exome
AF:
0.0879
Gnomad EAS exome
AF:
0.0369
Gnomad SAS exome
AF:
0.102
Gnomad FIN exome
AF:
0.0263
Gnomad NFE exome
AF:
0.0525
Gnomad OTH exome
AF:
0.0651
GnomAD4 exome
AF:
0.0535
AC:
75120
AN:
1403154
Hom.:
2425
Cov.:
35
AF XY:
0.0548
AC XY:
37965
AN XY:
692500
show subpopulations
Gnomad4 AFR exome
AF:
0.140
Gnomad4 AMR exome
AF:
0.0719
Gnomad4 ASJ exome
AF:
0.0887
Gnomad4 EAS exome
AF:
0.0300
Gnomad4 SAS exome
AF:
0.0992
Gnomad4 FIN exome
AF:
0.0285
Gnomad4 NFE exome
AF:
0.0473
Gnomad4 OTH exome
AF:
0.0655
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0749
AC:
11410
AN:
152298
Hom.:
535
Cov.:
34
AF XY:
0.0740
AC XY:
5510
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.136
Gnomad4 AMR
AF:
0.0765
Gnomad4 ASJ
AF:
0.0844
Gnomad4 EAS
AF:
0.0314
Gnomad4 SAS
AF:
0.0894
Gnomad4 FIN
AF:
0.0236
Gnomad4 NFE
AF:
0.0467
Gnomad4 OTH
AF:
0.0823
Alfa
AF:
0.0463
Hom.:
100
Bravo
AF:
0.0810
Asia WGS
AF:
0.0790
AC:
275
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMay 04, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.58
Cadd
Benign
0.73
Dann
Benign
0.94
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs5993890; hg19: chr22-19958829; COSMIC: COSV52889023; COSMIC: COSV52889023; API