rs887201

Positions:

• chr22-19989311-C-G

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARVCF	NM_001670.3	c.210+1274G>C		intron_variant		ENST00000263207.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARVCF	ENST00000263207.8	c.210+1274G>C		intron_variant		1	NM_001670.3	P4
ARVCF	ENST00000406259.1	c.210+1274G>C		intron_variant		5		A1
ARVCF	ENST00000467828.1	n.158-7220G>C		intron_variant, non_coding_transcript_variant		3
ARVCF	ENST00000473551.5	n.208+1274G>C		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.966

Gnomad4 AMR AF: 0.812

Gnomad4 ASJ AF: 0.959

Gnomad4 EAS AF: 0.588

Gnomad4 SAS AF: 0.882

Gnomad4 FIN AF: 0.864

Gnomad4 NFE AF: 0.946

Gnomad4 OTH AF: 0.923

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.48

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: rs887201; hg19: chr22-19976834;