rs2240714

Variant names:

• chr22-19973487-C-T
• rs2240714
• NM_001670.3:c.2239+156G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-19973487-C-T
• chr22-19973487-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001670.3(ARVCF):​c.2239+156G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.075 in 152,154 control chromosomes in the GnomAD database, including 542 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.075 (542 hom., cov: 34)
• Consequence: ARVCF NM_001670.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.43
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 22-19973487-C-T is Benign according to our data. Variant chr22-19973487-C-T is described in ClinVar as Benign. ClinVar VariationId is 1266945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.133 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.2239+156G>A		intron	N/A	NP_001661.1	O00192-1
	ARVCF	NM_001438684.1		c.2221+156G>A		intron	N/A	NP_001425613.1
	ARVCF	NM_001438685.1		c.2206+156G>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.2239+156G>A		intron	N/A	ENSP00000263207.3	O00192-1
	ARVCF	ENST00000406259.1	TSL:5	c.2221+156G>A		intron	N/A	ENSP00000385444.1	E9PDC3
	ARVCF	ENST00000852538.1		c.2206+156G>A		intron	N/A	ENSP00000522597.1

Frequencies

GnomAD3 genomes AF: 0.0748 AC: 11378 AN: 152036 Hom.: 536 Cov.: 34

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.0879

Gnomad AMR AF: 0.0766

Gnomad ASJ AF: 0.0844

Gnomad EAS AF: 0.0312

Gnomad SAS AF: 0.0893

Gnomad FIN AF: 0.0237

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0467

Gnomad OTH AF: 0.0826

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

GnomAD4 genome AF: 0.0750 AC: 11419 AN: 152154 Hom.: 542 Cov.: 34 AF XY: 0.0741 AC XY: 5511 AN XY: 74394

African (AFR) AF: 0.136 AC: 5666 AN: 41540

American (AMR) AF: 0.0765 AC: 1170 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0844 AC: 293 AN: 3472

East Asian (EAS) AF: 0.0307 AC: 158 AN: 5152

South Asian (SAS) AF: 0.0894 AC: 432 AN: 4832

European-Finnish (FIN) AF: 0.0237 AC: 251 AN: 10606

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0468 AC: 3176 AN: 67930

Other (OTH) AF: 0.0822 AC: 174 AN: 2116

Alfa AF: 0.0137 Hom.: 2

Bravo AF: 0.0810

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.88
DANN	Benign	0.81
PhyloP100		-1.4
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: rs2240714; hg19: chr22-19961010; COSMIC: COSV52890638; COSMIC: COSV52890638;