rs2239395

Variant names:

• chr22-19974680-T-G
• rs2239395
• NM_001670.3:c.1961-441A>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.1961-441A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,050 control chromosomes in the GnomAD database, including 2,502 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 0.13 (2502 hom., cov: 32)
• Consequence: ARVCF NM_001670.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.35
• Publications: 16 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARVCF	NM_001670.3	c.1961-441A>C		intron_variant	Intron 11 of 19	ENST00000263207.8	NP_001661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARVCF	ENST00000263207.8	c.1961-441A>C		intron_variant	Intron 11 of 19	1	NM_001670.3	ENSP00000263207.3

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19582 AN: 151932 Hom.: 2485 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0944

Gnomad ASJ AF: 0.0809

Gnomad EAS AF: 0.0316

Gnomad SAS AF: 0.0989

Gnomad FIN AF: 0.0150

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0450

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.129 AC: 19633 AN: 152050 Hom.: 2502 Cov.: 32 AF XY: 0.126 AC XY: 9336 AN XY: 74348

African (AFR) AF: 0.331 AC: 13712 AN: 41398

American (AMR) AF: 0.0942 AC: 1441 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0809 AC: 281 AN: 3472

East Asian (EAS) AF: 0.0311 AC: 161 AN: 5172

South Asian (SAS) AF: 0.0992 AC: 479 AN: 4830

European-Finnish (FIN) AF: 0.0150 AC: 159 AN: 10608

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0450 AC: 3056 AN: 67964

Other (OTH) AF: 0.124 AC: 262 AN: 2108

Alfa AF: 0.0676 Hom.: 1902

Bravo AF: 0.144

Asia WGS AF: 0.0860 AC: 302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.60
DANN	Benign	0.52
PhyloP100		-3.4
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: rs2239395; hg19: chr22-19962203;