chr22-19979545-G-A

Position:

• chr22-19979545-G-A

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.1396+198C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 817,398 control chromosomes in the GnomAD database, including 182,810 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (27556 hom., cov: 35)
  • Exomes 𝑓: 0.68 (155254 hom.)
• Consequence: ARVCF NM_001670.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.341

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 22-19979545-G-A is Benign according to our data. Variant chr22-19979545-G-A is described in ClinVar as [Benign]. Clinvar id is 1223805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARVCF	NM_001670.3	c.1396+198C>T		intron_variant		ENST00000263207.8	NP_001661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARVCF	ENST00000263207.8	c.1396+198C>T		intron_variant		1	NM_001670.3	ENSP00000263207	P4
ARVCF	ENST00000401994.5	c.1207+198C>T		intron_variant		5		ENSP00000384341
ARVCF	ENST00000406259.1	c.1396+198C>T		intron_variant		5		ENSP00000385444	A1
ARVCF	ENST00000406522.5	c.1207+198C>T		intron_variant		5		ENSP00000384732

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87807 AN: 152026 Hom.: 27563 Cov.: 35

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.602

GnomAD4 exome AF: 0.677 AC: 450177 AN: 665254 Hom.: 155254 AF XY: 0.673 AC XY: 226691 AN XY: 336826

Gnomad4 AFR exome AF: 0.322

Gnomad4 AMR exome AF: 0.543

Gnomad4 ASJ exome AF: 0.609

Gnomad4 EAS exome AF: 0.525

Gnomad4 SAS exome AF: 0.571

Gnomad4 FIN exome AF: 0.711

Gnomad4 NFE exome AF: 0.717

Gnomad4 OTH exome AF: 0.649

GnomAD4 genome AF: 0.577 AC: 87802 AN: 152144 Hom.: 27556 Cov.: 35 AF XY: 0.576 AC XY: 42821 AN XY: 74358

Gnomad4 AFR AF: 0.325

Gnomad4 AMR AF: 0.552

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.505

Gnomad4 SAS AF: 0.587

Gnomad4 FIN AF: 0.710

Gnomad4 NFE AF: 0.715

Gnomad4 OTH AF: 0.601

Alfa AF: 0.678 Hom.: 42321

Bravo AF: 0.554

Asia WGS AF: 0.542 AC: 1884 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	0.40
DANN	Benign	0.40

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: rs887204; hg19: chr22-19967068;