Variant rs5993890 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Clinical Significance

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

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]

ARVCF links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

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_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.23 with no splicing effect.

BA1

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	Protein	UniProt
ARVCF	NM_001670.3 linkuse as main transcript	c.2811C>T	p.Pro937=	synonymous_variant	19/20	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.2811C>T	p.Pro937=	synonymous_variant	19/20	1	NM_001670.3	ENSP00000263207	P4	O00192-1

Frequencies

GnomAD3 genomes

AF:

0.0747

AC:

11369

AN:

152180

Hom.:

529

Cov.:

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.:

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

AF:

0.0749

AC:

11410

AN:

152298

Hom.:

535

Cov.:

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: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	- -

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.

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