rs2518823

Positions:

• chr22-19972665-T-C
• chr22-19972665-T-G

Variant summary

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

The ENST00000263207.8(ARVCF):​c.2641+72A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.883 in 1,477,350 control chromosomes in the GnomAD database, including 579,842 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.86 (56769 hom., cov: 32)
  • Exomes 𝑓: 0.89 (523073 hom.)
• Consequence: ARVCF ENST00000263207.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.740

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=-0.93).
• BP6: Variant 22-19972665-T-C is Benign according to our data. Variant chr22-19972665-T-C is described in ClinVar as [Benign]. Clinvar id is 1266017.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	c.2641+72A>G		intron_variant		ENST00000263207.8	NP_001661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARVCF	ENST00000263207.8	c.2641+72A>G		intron_variant		1	NM_001670.3	ENSP00000263207	P4

Frequencies

GnomAD3 genomes AF: 0.860 AC: 130694 AN: 151988 Hom.: 56740 Cov.: 32

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.773

Gnomad ASJ AF: 0.936

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.907

Gnomad OTH AF: 0.875

GnomAD4 exome AF: 0.886 AC: 1173615 AN: 1325244 Hom.: 523073 AF XY: 0.885 AC XY: 575484 AN XY: 650192

Gnomad4 AFR exome AF: 0.853

Gnomad4 AMR exome AF: 0.694

Gnomad4 ASJ exome AF: 0.929

Gnomad4 EAS exome AF: 0.552

Gnomad4 SAS exome AF: 0.839

Gnomad4 FIN exome AF: 0.835

Gnomad4 NFE exome AF: 0.908

Gnomad4 OTH exome AF: 0.871

GnomAD4 genome AF: 0.860 AC: 130764 AN: 152106 Hom.: 56769 Cov.: 32 AF XY: 0.851 AC XY: 63291 AN XY: 74344

Gnomad4 AFR AF: 0.859

Gnomad4 AMR AF: 0.771

Gnomad4 ASJ AF: 0.936

Gnomad4 EAS AF: 0.535

Gnomad4 SAS AF: 0.828

Gnomad4 FIN AF: 0.818

Gnomad4 NFE AF: 0.907

Gnomad4 OTH AF: 0.873

Alfa AF: 0.882 Hom.: 7380

Bravo AF: 0.853

Asia WGS AF: 0.702 AC: 2445 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	clinical testing	GeneDx	May 10, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.4
DANN	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2518823; hg19: chr22-19960188;