rs165655

Positions:

• chr22-19970240-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000263207.8(ARVCF):​c.*516C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 989,364 control chromosomes in the GnomAD database, including 223,951 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 0.56 (25851 hom., cov: 33)
  • Exomes 𝑓: 0.68 (198100 hom.)
• Consequence: ARVCF ENST00000263207.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARVCF	NM_001670.3	c.*516C>T		3_prime_UTR_variant	20/20	ENST00000263207.8	NP_001661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARVCF	ENST00000263207.8	c.*516C>T		3_prime_UTR_variant	20/20	1	NM_001670.3	ENSP00000263207	P4
ARVCF	ENST00000495096.5	n.2207C>T		non_coding_transcript_exon_variant	12/12	2

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85007 AN: 151764 Hom.: 25857 Cov.: 33

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.796

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.580

GnomAD4 exome AF: 0.684 AC: 573154 AN: 837482 Hom.: 198100 Cov.: 71 AF XY: 0.685 AC XY: 265134 AN XY: 387198

Gnomad4 AFR exome AF: 0.288

Gnomad4 AMR exome AF: 0.507

Gnomad4 ASJ exome AF: 0.596

Gnomad4 EAS exome AF: 0.488

Gnomad4 SAS exome AF: 0.549

Gnomad4 FIN exome AF: 0.662

Gnomad4 NFE exome AF: 0.699

Gnomad4 OTH exome AF: 0.640

GnomAD4 genome AF: 0.560 AC: 85004 AN: 151882 Hom.: 25851 Cov.: 33 AF XY: 0.558 AC XY: 41423 AN XY: 74226

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.609

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.665

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.579

Alfa AF: 0.662 Hom.: 11791

Bravo AF: 0.539

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.52
DANN	Benign	0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs165655; hg19: chr22-19957763;