rs2518823

Variant names:

• chr22-19972665-T-C
• rs2518823
• NM_001670.3:c.2641+72A>G

Your query was ambiguous. Multiple possible variants found:

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

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.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 NM_001670.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.740
• Publications: 10 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=-0.93).
• BP6: Variant 22-19972665-T-C is Benign according to our data. Variant chr22-19972665-T-C is described in ClinVar as Benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
ARVCF	NM_001670.3	c.2641+72A>G		intron_variant	Intron 16 of 19	ENST00000263207.8	NP_001661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARVCF	ENST00000263207.8	c.2641+72A>G		intron_variant	Intron 16 of 19	1	NM_001670.3	ENSP00000263207.3

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

African (AFR) AF: 0.853 AC: 24760 AN: 29042

American (AMR) AF: 0.694 AC: 19353 AN: 27886

Ashkenazi Jewish (ASJ) AF: 0.929 AC: 18828 AN: 20264

East Asian (EAS) AF: 0.552 AC: 19680 AN: 35650

South Asian (SAS) AF: 0.839 AC: 58642 AN: 69936

European-Finnish (FIN) AF: 0.835 AC: 37638 AN: 45060

Middle Eastern (MID) AF: 0.909 AC: 4661 AN: 5128

European-Non Finnish (NFE) AF: 0.908 AC: 942187 AN: 1037348

Other (OTH) AF: 0.871 AC: 47866 AN: 54930

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

African (AFR) AF: 0.859 AC: 35641 AN: 41508

American (AMR) AF: 0.771 AC: 11779 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.936 AC: 3249 AN: 3472

East Asian (EAS) AF: 0.535 AC: 2755 AN: 5148

South Asian (SAS) AF: 0.828 AC: 3995 AN: 4824

European-Finnish (FIN) AF: 0.818 AC: 8655 AN: 10586

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.907 AC: 61658 AN: 67980

Other (OTH) AF: 0.873 AC: 1846 AN: 2114

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

-

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.4
DANN	Benign	0.49
PhyloP100		-0.74
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: rs2518823; hg19: chr22-19960188;