22-19970240-G-A

Variant names:

• chr22-19970240-G-A
• rs165655
• NM_001670.3:c.*516C>T

Variant summary

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

The NM_001670.3(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 NM_001670.3 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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ARVCF	NM_001670.3	c.*516C>T		3_prime_UTR_variant	Exon 20 of 20	ENST00000263207.8	NP_001661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARVCF	ENST00000263207	c.*516C>T		3_prime_UTR_variant	Exon 20 of 20	1	NM_001670.3	ENSP00000263207.3
ARVCF	ENST00000495096.5	n.2207C>T		non_coding_transcript_exon_variant	Exon 12 of 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 AC: 4570 AN: 15862

Gnomad4 AMR exome AF: 0.507 AC: 893 AN: 1760

Gnomad4 ASJ exome AF: 0.596 AC: 3091 AN: 5188

Gnomad4 EAS exome AF: 0.488 AC: 1926 AN: 3944

Gnomad4 SAS exome AF: 0.549 AC: 9333 AN: 16986

Gnomad4 FIN exome AF: 0.662 AC: 212 AN: 320

Gnomad4 NFE exome AF: 0.699 AC: 534562 AN: 764330

Gnomad4 Remaining exome AF: 0.640 AC: 17567 AN: 27464

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 AC: 0.315382 AN: 0.315382

Gnomad4 AMR AF: 0.540 AC: 0.539701 AN: 0.539701

Gnomad4 ASJ AF: 0.609 AC: 0.609222 AN: 0.609222

Gnomad4 EAS AF: 0.498 AC: 0.497629 AN: 0.497629

Gnomad4 SAS AF: 0.567 AC: 0.566653 AN: 0.566653

Gnomad4 FIN AF: 0.665 AC: 0.664995 AN: 0.664995

Gnomad4 NFE AF: 0.694 AC: 0.694323 AN: 0.694323

Gnomad4 OTH AF: 0.579 AC: 0.578997 AN: 0.578997

Alfa AF: 0.661 Hom.: 21513

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
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

Publications

LitVar

Other links and lift over

dbSNP: rs165655; hg19: chr22-19957763;