22-19973487-C-T

Position:

• chr22-19973487-C-T

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.2239+156G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.075 in 152,154 control chromosomes in the GnomAD database, including 542 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.075 (542 hom., cov: 34)
• Consequence: ARVCF ENST00000263207.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.43

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=-0.86).
• BP6: Variant 22-19973487-C-T is Benign according to our data. Variant chr22-19973487-C-T is described in ClinVar as [Benign]. Clinvar id is 1266945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARVCF	NM_001670.3	c.2239+156G>A		intron_variant		ENST00000263207.8	NP_001661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARVCF	ENST00000263207.8	c.2239+156G>A		intron_variant		1	NM_001670.3	ENSP00000263207	P4

Frequencies

GnomAD3 genomes AF: 0.0748 AC: 11378 AN: 152036 Hom.: 536 Cov.: 34

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.0879

Gnomad AMR AF: 0.0766

Gnomad ASJ AF: 0.0844

Gnomad EAS AF: 0.0312

Gnomad SAS AF: 0.0893

Gnomad FIN AF: 0.0237

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0467

Gnomad OTH AF: 0.0826

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0750 AC: 11419 AN: 152154 Hom.: 542 Cov.: 34 AF XY: 0.0741 AC XY: 5511 AN XY: 74394

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.0765

Gnomad4 ASJ AF: 0.0844

Gnomad4 EAS AF: 0.0307

Gnomad4 SAS AF: 0.0894

Gnomad4 FIN AF: 0.0237

Gnomad4 NFE AF: 0.0468

Gnomad4 OTH AF: 0.0822

Alfa AF: 0.0137 Hom.: 2

Bravo AF: 0.0810

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	-0.86
CADD	Benign	0.88
DANN	Benign	0.81

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: rs2240714; hg19: chr22-19961010; COSMIC: COSV52890638; COSMIC: COSV52890638;