Variant 22-19971288-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BS1BS2

The NM_001670.3(ARVCF):c.2829G>A(p.Ala943Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0238 in 1,557,012 control chromosomes in the GnomAD database, including 536 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 0.017 ( 37 hom., cov: 34)

Exomes 𝑓: 0.025 ( 499 hom. )

Consequence

ARVCF
NM_001670.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.31

Variant links:

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]

ARVCF links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP7

Synonymous conserved (PhyloP=-2.31 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0172 (2613/152328) while in subpopulation NFE AF= 0.0283 (1924/68030). AF 95% confidence interval is 0.0272. There are 37 homozygotes in gnomad4. There are 1156 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARVCF	NM_001670.3 link	c.2829G>A	p.Ala943Ala	synonymous_variant	19/20	ENST00000263207.8	NP_001661.1	O00192-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARVCF	ENST00000263207.8 link	c.2829G>A	p.Ala943Ala	synonymous_variant	19/20	1	NM_001670.3	ENSP00000263207.3		O00192-1

Frequencies

GnomAD3 genomes

AF:

0.0172

AC:

2613

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00458

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0173

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00951

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0283

Gnomad OTH

AF:

0.0234

GnomAD3 exomes

AF:

0.0165

AC:

2695

AN:

163106

Hom.:

AF XY:

0.0170

AC XY:

1468

AN XY:

86332

show subpopulations

Gnomad AFR exome

AF:

0.00440

Gnomad AMR exome

AF:

0.0119

Gnomad ASJ exome

AF:

0.0172

Gnomad EAS exome

AF:

0.0000814

Gnomad SAS exome

AF:

0.00218

Gnomad FIN exome

AF:

0.00954

Gnomad NFE exome

AF:

0.0301

Gnomad OTH exome

AF:

0.0164

GnomAD4 exome

AF:

0.0245

AC:

34418

AN:

1404684

Hom.:

499

Cov.:

AF XY:

0.0238

AC XY:

16489

AN XY:

693340

show subpopulations

Gnomad4 AFR exome

AF:

0.00398

Gnomad4 AMR exome

AF:

0.0121

Gnomad4 ASJ exome

AF:

0.0153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00209

Gnomad4 FIN exome

AF:

0.0100

Gnomad4 NFE exome

AF:

0.0290

Gnomad4 OTH exome

AF:

0.0223

GnomAD4 genome

AF:

0.0172

AC:

2613

AN:

152328

Hom.:

Cov.:

AF XY:

0.0155

AC XY:

1156

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00457

Gnomad4 AMR

AF:

0.0173

Gnomad4 ASJ

AF:

0.0144

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00951

Gnomad4 NFE

AF:

0.0283

Gnomad4 OTH

AF:

0.0232

Alfa

AF:

0.0221

Hom.:

Bravo

AF:

0.0180

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

1.0

DANN

Benign

0.95

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over