chr22-19971488-G-A

Variant names:

• chr22-19971488-G-A
• rs13056165
• NM_001670.3:c.2782-153C>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.2782-153C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,230 control chromosomes in the GnomAD database, including 1,663 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (1663 hom., cov: 34)
• Consequence: ARVCF NM_001670.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.40
• 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=-0.81).
• BP6: Variant 22-19971488-G-A is Benign according to our data. Variant chr22-19971488-G-A is described in ClinVar as Benign. ClinVar VariationId is 1277085.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.181 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.2782-153C>T		intron	N/A	NP_001661.1	O00192-1
	ARVCF	NM_001438684.1		c.2764-153C>T		intron	N/A	NP_001425613.1
	ARVCF	NM_001438685.1		c.2749-153C>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.2782-153C>T		intron	N/A	ENSP00000263207.3	O00192-1
	ARVCF	ENST00000406259.1	TSL:5	c.2764-153C>T		intron	N/A	ENSP00000385444.1	E9PDC3
	ARVCF	ENST00000852538.1		c.2749-153C>T		intron	N/A	ENSP00000522597.1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19718 AN: 152112 Hom.: 1664 Cov.: 34

Gnomad AFR AF: 0.0284

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.0988

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.130 AC: 19714 AN: 152230 Hom.: 1663 Cov.: 34 AF XY: 0.135 AC XY: 10076 AN XY: 74432

African (AFR) AF: 0.0283 AC: 1175 AN: 41556

American (AMR) AF: 0.160 AC: 2455 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0988 AC: 343 AN: 3472

East Asian (EAS) AF: 0.119 AC: 615 AN: 5178

South Asian (SAS) AF: 0.191 AC: 924 AN: 4828

European-Finnish (FIN) AF: 0.277 AC: 2937 AN: 10608

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10745 AN: 67966

Other (OTH) AF: 0.123 AC: 259 AN: 2112

Alfa AF: 0.156 Hom.: 299

Bravo AF: 0.115

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	-0.81
CADD	Benign	6.8
DANN	Benign	0.71
PhyloP100		1.4
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: rs13056165; hg19: chr22-19959011;