rs887201

Variant names:

• chr22-19989311-C-G
• rs887201
• NM_001670.3:c.210+1274G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001670.3(ARVCF):​c.210+1274G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.918 in 152,122 control chromosomes in the GnomAD database, including 64,670 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.92 (64670 hom., cov: 30)
• Consequence: ARVCF NM_001670.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.422
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.958 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.210+1274G>C		intron	N/A	NP_001661.1
	ARVCF	NM_001438684.1		c.210+1274G>C		intron	N/A	NP_001425613.1
	ARVCF	NM_001438685.1		c.210+1274G>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.210+1274G>C		intron	N/A	ENSP00000263207.3
	ARVCF	ENST00000406259.1	TSL:5	c.210+1274G>C		intron	N/A	ENSP00000385444.1
	ARVCF	ENST00000467828.1	TSL:3	n.158-7220G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.918 AC: 139552 AN: 152004 Hom.: 64625 Cov.: 30

Gnomad AFR AF: 0.966

Gnomad AMI AF: 0.976

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.959

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.883

Gnomad FIN AF: 0.864

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.946

Gnomad OTH AF: 0.925

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

GnomAD4 genome AF: 0.918 AC: 139648 AN: 152122 Hom.: 64670 Cov.: 30 AF XY: 0.910 AC XY: 67659 AN XY: 74360

African (AFR) AF: 0.966 AC: 40077 AN: 41508

American (AMR) AF: 0.812 AC: 12404 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.959 AC: 3327 AN: 3468

East Asian (EAS) AF: 0.588 AC: 3029 AN: 5154

South Asian (SAS) AF: 0.882 AC: 4253 AN: 4820

European-Finnish (FIN) AF: 0.864 AC: 9152 AN: 10598

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.946 AC: 64286 AN: 67980

Other (OTH) AF: 0.923 AC: 1947 AN: 2110

Alfa AF: 0.926 Hom.: 8133

Bravo AF: 0.913

Asia WGS AF: 0.751 AC: 2614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.48
PhyloP100		-0.42
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: rs887201; hg19: chr22-19976834;