rs165824

Positions:

• chr22-19971843-G-A
• chr22-19971843-G-C
• chr22-19971843-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.57

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]

ACMG classification

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	UniProt
ARVCF	NM_001670.3	c.2781+43C>T		intron_variant		ENST00000263207.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARVCF	ENST00000263207.8	c.2781+43C>T		intron_variant		1	NM_001670.3	P4

Frequencies

GnomAD3 genomes AF: 0.866 AC: 131715 AN: 152090 Hom.: 57589 Cov.: 34

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

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.: 28 AF XY: 0.882 AC XY: 636659 AN XY: 721574

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.: 34 AF XY: 0.858 AC XY: 63827 AN XY: 74424

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

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

Other links and lift over

dbSNP: rs165824; hg19: chr22-19959366;