rs12329964

Variant names:

• chr22-19971510-G-A
• rs12329964
• NM_001670.3:c.2782-175C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001670.3(ARVCF):​c.2782-175C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,246 control chromosomes in the GnomAD database, including 1,787 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (1787 hom., cov: 34)
• Consequence: ARVCF NM_001670.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.117
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 22-19971510-G-A is Benign according to our data. Variant chr22-19971510-G-A is described in ClinVar as Benign. ClinVar VariationId is 1243428.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.162 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.2782-175C>T		intron	N/A	NP_001661.1	O00192-1
	ARVCF	NM_001438684.1		c.2764-175C>T		intron	N/A	NP_001425613.1
	ARVCF	NM_001438685.1		c.2749-175C>T		intron	N/A	NP_001425614.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARVCF	ENST00000263207.8	TSL:1 MANE Select	c.2782-175C>T		intron	N/A	ENSP00000263207.3	O00192-1
	ARVCF	ENST00000406259.1	TSL:5	c.2764-175C>T		intron	N/A	ENSP00000385444.1	E9PDC3
	ARVCF	ENST00000852538.1		c.2749-175C>T		intron	N/A	ENSP00000522597.1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22342 AN: 152128 Hom.: 1786 Cov.: 34

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.151

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.147 AC: 22350 AN: 152246 Hom.: 1787 Cov.: 34 AF XY: 0.144 AC XY: 10704 AN XY: 74434

African (AFR) AF: 0.140 AC: 5799 AN: 41548

American (AMR) AF: 0.127 AC: 1936 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 827 AN: 3472

East Asian (EAS) AF: 0.00308 AC: 16 AN: 5188

South Asian (SAS) AF: 0.157 AC: 759 AN: 4830

European-Finnish (FIN) AF: 0.127 AC: 1352 AN: 10612

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.164 AC: 11176 AN: 67984

Other (OTH) AF: 0.151 AC: 319 AN: 2110

Alfa AF: 0.161 Hom.: 248

Bravo AF: 0.144

Asia WGS AF: 0.0790 AC: 276 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.58
PhyloP100		0.12
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)		0.010		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: rs12329964; hg19: chr22-19959033;