chr22-19974432-A-G

Variant names:

• chr22-19974432-A-G
• rs887199
• NM_001670.3:c.1961-193T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001670.3(ARVCF):​c.1961-193T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 152,048 control chromosomes in the GnomAD database, including 41,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.72 (41490 hom., cov: 32)
• Consequence: ARVCF NM_001670.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.111
• Publications: 14 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 22-19974432-A-G is Benign according to our data. Variant chr22-19974432-A-G is described in ClinVar as Benign. ClinVar VariationId is 1238346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.854 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARVCF	NM_001670.3	MANE Select	c.1961-193T>C		intron	N/A	NP_001661.1
	ARVCF	NM_001438684.1		c.1943-193T>C		intron	N/A	NP_001425613.1
	ARVCF	NM_001438685.1		c.1928-193T>C		intron	N/A	NP_001425614.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARVCF	ENST00000263207.8	TSL:1 MANE Select	c.1961-193T>C		intron	N/A	ENSP00000263207.3
	ARVCF	ENST00000406259.1	TSL:5	c.1943-193T>C		intron	N/A	ENSP00000385444.1
	ARVCF	ENST00000401994.5	TSL:5	c.1772-193T>C		intron	N/A	ENSP00000384341.1

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109512 AN: 151930 Hom.: 41487 Cov.: 32

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.909

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.847

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.794

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.860

Gnomad OTH AF: 0.746

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

GnomAD4 genome AF: 0.720 AC: 109530 AN: 152048 Hom.: 41490 Cov.: 32 AF XY: 0.716 AC XY: 53178 AN XY: 74318

African (AFR) AF: 0.498 AC: 20624 AN: 41432

American (AMR) AF: 0.675 AC: 10307 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.847 AC: 2939 AN: 3468

East Asian (EAS) AF: 0.502 AC: 2589 AN: 5158

South Asian (SAS) AF: 0.731 AC: 3517 AN: 4814

European-Finnish (FIN) AF: 0.794 AC: 8411 AN: 10590

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.860 AC: 58484 AN: 67992

Other (OTH) AF: 0.745 AC: 1573 AN: 2112

Alfa AF: 0.815 Hom.: 79347

Bravo AF: 0.699

Asia WGS AF: 0.617 AC: 2148 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

May 10, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.9
DANN	Benign	0.69
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs887199; hg19: chr22-19961955;