Variant chr22-19971843-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001670.3(ARVCF):c.2781+43C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.881 in 1,600,910 control chromosomes in the GnomAD database, including 625,658 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.87 ( 57615 hom., cov: 34)

Exomes 𝑓: 0.88 ( 568043 hom. )

Consequence

ARVCF
NM_001670.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.57

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 22-19971843-G-A is Benign according to our data. Variant chr22-19971843-G-A is described in ClinVar as [Benign]. Clinvar id is 1287158.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.901 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.2781+43C>T		intron_variant		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.2781+43C>T		intron_variant		1	NM_001670.3	ENSP00000263207	P4	O00192-1

Frequencies

GnomAD3 genomes

AF:

0.866

AC:

131715

AN:

152090

Hom.:

57589

Cov.:

show subpopulations

Gnomad AFR

AF:

0.881

Gnomad AMI

AF:

0.997

Gnomad AMR

AF:

0.776

Gnomad ASJ

AF:

0.936

Gnomad EAS

AF:

0.534

Gnomad SAS

AF:

0.829

Gnomad FIN

AF:

0.818

Gnomad MID

AF:

0.937

Gnomad NFE

AF:

0.907

Gnomad OTH

AF:

0.880

GnomAD3 exomes

AF:

0.830

AC:

206832

AN:

249254

Hom.:

87679

AF XY:

0.839

AC XY:

113288

AN XY:

135024

show subpopulations

Gnomad AFR exome

AF:

0.880

Gnomad AMR exome

AF:

0.664

Gnomad ASJ exome

AF:

0.932

Gnomad EAS exome

AF:

0.536

Gnomad SAS exome

AF:

0.834

Gnomad FIN exome

AF:

0.824

Gnomad NFE exome

AF:

0.910

Gnomad OTH exome

AF:

0.862

GnomAD4 exome

AF:

0.882

AC:

1278088

AN:

1448702

Hom.:

568043

Cov.:

AF XY:

0.882

AC XY:

636659

AN XY:

721574

show subpopulations

Gnomad4 AFR exome

AF:

0.876

Gnomad4 AMR exome

AF:

0.675

Gnomad4 ASJ exome

AF:

0.931

Gnomad4 EAS exome

AF:

0.551

Gnomad4 SAS exome

AF:

0.837

Gnomad4 FIN exome

AF:

0.833

Gnomad4 NFE exome

AF:

0.908

Gnomad4 OTH exome

AF:

0.873

GnomAD4 genome

AF:

0.866

AC:

131781

AN:

152208

Hom.:

57615

Cov.:

AF XY:

0.858

AC XY:

63827

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.880

Gnomad4 AMR

AF:

0.775

Gnomad4 ASJ

AF:

0.936

Gnomad4 EAS

AF:

0.534

Gnomad4 SAS

AF:

0.828

Gnomad4 FIN

AF:

0.818

Gnomad4 NFE

AF:

0.907

Gnomad4 OTH

AF:

0.878

Alfa

AF:

0.896

Hom.:

60413

Bravo

AF:

0.860

Asia WGS

AF:

0.704

AC:

2450

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 10, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.11

DANN

Benign

0.44

RBP_binding_hub_radar

0.85

RBP_regulation_power_radar

2.0

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