rs9265

Positions:

• chr22-19970108-C-A

Variant summary

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

The NM_001670.3(ARVCF):​c.*648G>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 985,340 control chromosomes in the GnomAD database, including 223,113 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 (25905 hom., cov: 32)
  • Exomes 𝑓: 0.68 (197208 hom.)
• Consequence: ARVCF NM_001670.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890

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=-0.86).
• 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.*648G>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.*648G>T		3_prime_UTR_variant	20/20	1	NM_001670.3	ENSP00000263207	P4
ARVCF	ENST00000495096.5	n.2339G>T		non_coding_transcript_exon_variant	12/12	2

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85124 AN: 151922 Hom.: 25912 Cov.: 32

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: 0.666

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.581

GnomAD4 exome AF: 0.685 AC: 570500 AN: 833300 Hom.: 197208 Cov.: 60 AF XY: 0.685 AC XY: 263644 AN XY: 384838

Gnomad4 AFR exome AF: 0.288

Gnomad4 AMR exome AF: 0.505

Gnomad4 ASJ exome AF: 0.596

Gnomad4 EAS exome AF: 0.490

Gnomad4 SAS exome AF: 0.550

Gnomad4 FIN exome AF: 0.662

Gnomad4 NFE exome AF: 0.699

Gnomad4 OTH exome AF: 0.639

GnomAD4 genome AF: 0.560 AC: 85119 AN: 152040 Hom.: 25905 Cov.: 32 AF XY: 0.558 AC XY: 41498 AN XY: 74310

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.609

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.666

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.580

Alfa AF: 0.684 Hom.: 25276

Bravo AF: 0.539

Asia WGS AF: 0.529 AC: 1842 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.9
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs9265; hg19: chr22-19957631;