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
• Publications: 13 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.689 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARVCF	NM_001670.3	MANE Select	c.*516C>T		3_prime_UTR	Exon 20 of 20	NP_001661.1	O00192-1
	ARVCF	NM_001438684.1		c.*988C>T		3_prime_UTR	Exon 18 of 18	NP_001425613.1
	ARVCF	NM_001438685.1		c.*878C>T		3_prime_UTR	Exon 19 of 19	NP_001425614.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARVCF	ENST00000263207.8	TSL:1 MANE Select	c.*516C>T		3_prime_UTR	Exon 20 of 20	ENSP00000263207.3	O00192-1
	ARVCF	ENST00000852538.1		c.*516C>T		3_prime_UTR	Exon 19 of 19	ENSP00000522597.1
	ARVCF	ENST00000934103.1		c.*516C>T		3_prime_UTR	Exon 18 of 18	ENSP00000604162.1

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

African (AFR) AF: 0.288 AC: 4570 AN: 15862

American (AMR) AF: 0.507 AC: 893 AN: 1760

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 3091 AN: 5188

East Asian (EAS) AF: 0.488 AC: 1926 AN: 3944

South Asian (SAS) AF: 0.549 AC: 9333 AN: 16986

European-Finnish (FIN) AF: 0.662 AC: 212 AN: 320

Middle Eastern (MID) AF: 0.614 AC: 1000 AN: 1628

European-Non Finnish (NFE) AF: 0.699 AC: 534562 AN: 764330

Other (OTH) 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

African (AFR) AF: 0.315 AC: 13077 AN: 41464

American (AMR) AF: 0.540 AC: 8238 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 2114 AN: 3470

East Asian (EAS) AF: 0.498 AC: 2519 AN: 5062

South Asian (SAS) AF: 0.567 AC: 2729 AN: 4816

European-Finnish (FIN) AF: 0.665 AC: 7029 AN: 10570

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47157 AN: 67918

Other (OTH) AF: 0.579 AC: 1224 AN: 2114

Alfa AF: 0.661 Hom.: 21513

Bravo AF: 0.539

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.52
DANN	Benign	0.45
PhyloP100		-0.23
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

Other links and lift over

dbSNP: rs165655; hg19: chr22-19957763;