22-19974857-C-T

Variant names:

• chr22-19974857-C-T
• rs1110477
• NM_001670.3:c.1961-618G>A

Variant summary

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

The NM_001670.3(ARVCF):​c.1961-618G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.898 in 152,106 control chromosomes in the GnomAD database, including 61,878 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 0.90 (61878 hom., cov: 31)
• Consequence: ARVCF NM_001670.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARVCF	NM_001670.3	c.1961-618G>A		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.1961-618G>A		intron_variant	Intron 11 of 19	1	NM_001670.3	ENSP00000263207.3

Frequencies

GnomAD3 genomes AF: 0.899 AC: 136567 AN: 151988 Hom.: 61858 Cov.: 31

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.976

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.959

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.884

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.945

Gnomad OTH AF: 0.915

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

GnomAD4 genome AF: 0.898 AC: 136633 AN: 152106 Hom.: 61878 Cov.: 31 AF XY: 0.891 AC XY: 66226 AN XY: 74360

African (AFR) AF: 0.894 AC: 37088 AN: 41478

American (AMR) AF: 0.810 AC: 12382 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.959 AC: 3329 AN: 3472

East Asian (EAS) AF: 0.601 AC: 3099 AN: 5156

South Asian (SAS) AF: 0.883 AC: 4252 AN: 4814

European-Finnish (FIN) AF: 0.861 AC: 9130 AN: 10598

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.945 AC: 64263 AN: 67988

Other (OTH) AF: 0.913 AC: 1926 AN: 2110

Alfa AF: 0.896 Hom.: 23215

Bravo AF: 0.891

Asia WGS AF: 0.751 AC: 2615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.17
DANN	Benign	0.64
PhyloP100		-2.1
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: rs1110477; hg19: chr22-19962380;