chr22-19976143-C-T

Position:

• chr22-19976143-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001670.3(ARVCF):​c.1889-386G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,052 control chromosomes in the GnomAD database, including 43,819 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 0.74 (43819 hom., cov: 32)
• Consequence: ARVCF NM_001670.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.946

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARVCF	NM_001670.3	c.1889-386G>A		intron_variant		ENST00000263207.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARVCF	ENST00000263207.8	c.1889-386G>A		intron_variant		1	NM_001670.3	P4

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112595 AN: 151934 Hom.: 43818 Cov.: 32

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.862

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.881

Gnomad OTH AF: 0.766

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

GnomAD4 genome AF: 0.741 AC: 112612 AN: 152052 Hom.: 43819 Cov.: 32 AF XY: 0.736 AC XY: 54709 AN XY: 74318

Gnomad4 AFR AF: 0.516

Gnomad4 AMR AF: 0.693

Gnomad4 ASJ AF: 0.862

Gnomad4 EAS AF: 0.502

Gnomad4 SAS AF: 0.745

Gnomad4 FIN AF: 0.840

Gnomad4 NFE AF: 0.881

Gnomad4 OTH AF: 0.764

Alfa AF: 0.838 Hom.: 53010

Bravo AF: 0.717

Asia WGS AF: 0.624 AC: 2171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.82
DANN	Benign	0.56

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: rs887200; hg19: chr22-19963666;