22-20002119-A-G

Variant names:

• chr22-20002119-A-G
• rs2073742
• NM_001670.3:c.-19+8336T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001670.3(ARVCF):​c.-19+8336T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,230 control chromosomes in the GnomAD database, including 8,346 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 0.30 (8346 hom., cov: 33)
• Consequence: ARVCF NM_001670.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390
• Publications: 8 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARVCF	NM_001670.3	c.-19+8336T>C		intron_variant	Intron 2 of 19	ENST00000263207.8	NP_001661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARVCF	ENST00000263207.8	c.-19+8336T>C		intron_variant	Intron 2 of 19	1	NM_001670.3	ENSP00000263207.3
ARVCF	ENST00000467828.1	n.157+14470T>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45500 AN: 152112 Hom.: 8318 Cov.: 33

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.299 AC: 45578 AN: 152230 Hom.: 8346 Cov.: 33 AF XY: 0.295 AC XY: 21924 AN XY: 74412

African (AFR) AF: 0.514 AC: 21355 AN: 41522

American (AMR) AF: 0.258 AC: 3954 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1100 AN: 3470

East Asian (EAS) AF: 0.102 AC: 530 AN: 5190

South Asian (SAS) AF: 0.256 AC: 1236 AN: 4820

European-Finnish (FIN) AF: 0.187 AC: 1987 AN: 10604

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14493 AN: 68000

Other (OTH) AF: 0.287 AC: 605 AN: 2110

Alfa AF: 0.247 Hom.: 16634

Bravo AF: 0.314

Asia WGS AF: 0.195 AC: 682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.9
DANN	Benign	0.31
PhyloP100		-0.039
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: rs2073742; hg19: chr22-19989642;