chr22-19971704-G-A

Variant names:

• chr22-19971704-G-A
• rs62223683
• NM_001670.3:c.2781+182C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001670.3(ARVCF):​c.2781+182C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0586 in 152,284 control chromosomes in the GnomAD database, including 378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.059 (378 hom., cov: 34)
• Consequence: ARVCF NM_001670.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.312
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 22-19971704-G-A is Benign according to our data. Variant chr22-19971704-G-A is described in ClinVar as Benign. ClinVar VariationId is 1297923.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0892 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001670.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARVCF	NM_001670.3	MANE Select	c.2781+182C>T		intron	N/A	NP_001661.1	O00192-1
	ARVCF	NM_001438684.1		c.2763+182C>T		intron	N/A	NP_001425613.1
	ARVCF	NM_001438685.1		c.2748+182C>T		intron	N/A	NP_001425614.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARVCF	ENST00000263207.8	TSL:1 MANE Select	c.2781+182C>T		intron	N/A	ENSP00000263207.3	O00192-1
	ARVCF	ENST00000406259.1	TSL:5	c.2763+182C>T		intron	N/A	ENSP00000385444.1	E9PDC3
	ARVCF	ENST00000852538.1		c.2748+182C>T		intron	N/A	ENSP00000522597.1

Frequencies

GnomAD3 genomes AF: 0.0587 AC: 8929 AN: 152166 Hom.: 378 Cov.: 34

Gnomad AFR AF: 0.0181

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0703

Gnomad ASJ AF: 0.0850

Gnomad EAS AF: 0.00269

Gnomad SAS AF: 0.0400

Gnomad FIN AF: 0.0203

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0911

Gnomad OTH AF: 0.0660

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

GnomAD4 genome AF: 0.0586 AC: 8922 AN: 152284 Hom.: 378 Cov.: 34 AF XY: 0.0551 AC XY: 4099 AN XY: 74452

African (AFR) AF: 0.0180 AC: 750 AN: 41562

American (AMR) AF: 0.0701 AC: 1072 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0850 AC: 295 AN: 3470

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5186

South Asian (SAS) AF: 0.0402 AC: 194 AN: 4826

European-Finnish (FIN) AF: 0.0203 AC: 216 AN: 10626

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0911 AC: 6193 AN: 67994

Other (OTH) AF: 0.0653 AC: 138 AN: 2114

Alfa AF: 0.0559 Hom.: 142

Bravo AF: 0.0624

Asia WGS AF: 0.0240 AC: 85 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.38
PhyloP100		-0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs62223683; hg19: chr22-19959227;