dbSNP rs5993891: ARVCF:c.2695+135G>A (chr22-19972223-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001670.3(ARVCF):c.2695+135G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0704 in 1,230,822 control chromosomes in the GnomAD database, including 6,606 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 2925 hom., cov: 33)

Exomes 𝑓: 0.061 ( 3681 hom. )

Consequence

ARVCF
NM_001670.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.17

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 (BayesDel_noAF=-0.85).

BP6

Variant 22-19972223-C-T is Benign according to our data. Variant chr22-19972223-C-T is described in ClinVar as [Benign]. Clinvar id is 1233397.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARVCF	NM_001670.3 link	c.2695+135G>A		intron_variant	Intron 17 of 19	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.2695+135G>A		intron_variant	Intron 17 of 19	1	NM_001670.3	ENSP00000263207.3		O00192-1

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21193

AN:

152058

Hom.:

2908

Cov.:

show subpopulations

Gnomad AFR

AF:

0.359

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.0973

Gnomad ASJ

AF:

0.0888

Gnomad EAS

AF:

0.0320

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.0236

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0479

Gnomad OTH

AF:

0.132

GnomAD4 exome

AF:

0.0607

AC:

65453

AN:

1078646

Hom.:

3681

AF XY:

0.0616

AC XY:

33369

AN XY:

541514

show subpopulations

Gnomad4 AFR exome

AF:

0.364

Gnomad4 AMR exome

AF:

0.0827

Gnomad4 ASJ exome

AF:

0.0941

Gnomad4 EAS exome

AF:

0.0298

Gnomad4 SAS exome

AF:

0.111

Gnomad4 FIN exome

AF:

0.0285

Gnomad4 NFE exome

AF:

0.0467

Gnomad4 OTH exome

AF:

0.0812

GnomAD4 genome

AF:

0.140

AC:

21246

AN:

152176

Hom.:

2925

Cov.:

AF XY:

0.136

AC XY:

10113

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.360

Gnomad4 AMR

AF:

0.0971

Gnomad4 ASJ

AF:

0.0888

Gnomad4 EAS

AF:

0.0315

Gnomad4 SAS

AF:

0.104

Gnomad4 FIN

AF:

0.0236

Gnomad4 NFE

AF:

0.0479

Gnomad4 OTH

AF:

0.131

Alfa

AF:

0.0673

Hom.:

810

Bravo

AF:

0.154

Asia WGS

AF:

0.0890

AC:

313

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 10, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.44

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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