22-19975246-C-T

Variant names:

• chr22-19975246-C-T
• rs1110478
• NM_001670.3:c.1960+440G>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.1960+440G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 152,062 control chromosomes in the GnomAD database, including 43,721 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 (43721 hom., cov: 34)
• Consequence: ARVCF NM_001670.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660
• Publications: 3 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001670.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARVCF	NM_001670.3	MANE Select	c.1960+440G>A		intron	N/A	NP_001661.1
	ARVCF	NM_001438684.1		c.1942+440G>A		intron	N/A	NP_001425613.1
	ARVCF	NM_001438685.1		c.1927+440G>A		intron	N/A	NP_001425614.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARVCF	ENST00000263207.8	TSL:1 MANE Select	c.1960+440G>A		intron	N/A	ENSP00000263207.3
	ARVCF	ENST00000406259.1	TSL:5	c.1942+440G>A		intron	N/A	ENSP00000385444.1
	ARVCF	ENST00000852538.1		c.1927+440G>A		intron	N/A	ENSP00000522597.1

Frequencies

GnomAD3 genomes AF: 0.740 AC: 112427 AN: 151944 Hom.: 43720 Cov.: 34

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.862

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.839

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: 0.739 AC: 112444 AN: 152062 Hom.: 43721 Cov.: 34 AF XY: 0.735 AC XY: 54621 AN XY: 74314

African (AFR) AF: 0.512 AC: 21213 AN: 41452

American (AMR) AF: 0.693 AC: 10586 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.862 AC: 2990 AN: 3470

East Asian (EAS) AF: 0.503 AC: 2588 AN: 5144

South Asian (SAS) AF: 0.745 AC: 3595 AN: 4826

European-Finnish (FIN) AF: 0.839 AC: 8877 AN: 10582

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.881 AC: 59896 AN: 67988

Other (OTH) AF: 0.764 AC: 1614 AN: 2112

Alfa AF: 0.776 Hom.: 7493

Bravo AF: 0.716

Asia WGS AF: 0.624 AC: 2172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.7
DANN	Benign	0.58
PhyloP100		-0.066
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: rs1110478; hg19: chr22-19962769; COSMIC: COSV54267524; COSMIC: COSV54267524;