rs165824

Variant names:

• chr22-19971843-G-A
• rs165824
• NM_001670.3:c.2781+43C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-19971843-G-A
• chr22-19971843-G-C
• chr22-19971843-G-T

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.2781+43C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.881 in 1,600,910 control chromosomes in the GnomAD database, including 625,658 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.87 (57615 hom., cov: 34)
  • Exomes 𝑓: 0.88 (568043 hom.)
• Consequence: ARVCF NM_001670.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.57
• Publications: 11 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=-0.96).
• BP6: Variant 22-19971843-G-A is Benign according to our data. Variant chr22-19971843-G-A is described in ClinVar as [Benign]. Clinvar id is 1287158.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARVCF	NM_001670.3	c.2781+43C>T		intron_variant	Intron 18 of 19	ENST00000263207.8	NP_001661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARVCF	ENST00000263207.8	c.2781+43C>T		intron_variant	Intron 18 of 19	1	NM_001670.3	ENSP00000263207.3

Frequencies

GnomAD3 genomes AF: 0.866 AC: 131715 AN: 152090 Hom.: 57589 Cov.: 34

Gnomad AFR AF: 0.881

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.936

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.907

Gnomad OTH AF: 0.880

GnomAD2 exomes AF: 0.830 AC: 206832 AN: 249254 AF XY: 0.839

Gnomad AFR exome AF: 0.880

Gnomad AMR exome AF: 0.664

Gnomad ASJ exome AF: 0.932

Gnomad EAS exome AF: 0.536

Gnomad FIN exome AF: 0.824

Gnomad NFE exome AF: 0.910

Gnomad OTH exome AF: 0.862

GnomAD4 exome AF: 0.882 AC: 1278088 AN: 1448702 Hom.: 568043 Cov.: 28 AF XY: 0.882 AC XY: 636659 AN XY: 721574

African (AFR) AF: 0.876 AC: 29135 AN: 33266

American (AMR) AF: 0.675 AC: 30132 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.931 AC: 24213 AN: 26016

East Asian (EAS) AF: 0.551 AC: 21852 AN: 39626

South Asian (SAS) AF: 0.837 AC: 72025 AN: 86014

European-Finnish (FIN) AF: 0.833 AC: 43303 AN: 51964

Middle Eastern (MID) AF: 0.912 AC: 5238 AN: 5742

European-Non Finnish (NFE) AF: 0.908 AC: 999817 AN: 1101474

Other (OTH) AF: 0.873 AC: 52373 AN: 59986

GnomAD4 genome AF: 0.866 AC: 131781 AN: 152208 Hom.: 57615 Cov.: 34 AF XY: 0.858 AC XY: 63827 AN XY: 74424

African (AFR) AF: 0.880 AC: 36551 AN: 41520

American (AMR) AF: 0.775 AC: 11850 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.936 AC: 3249 AN: 3472

East Asian (EAS) AF: 0.534 AC: 2759 AN: 5168

South Asian (SAS) AF: 0.828 AC: 4002 AN: 4832

European-Finnish (FIN) AF: 0.818 AC: 8678 AN: 10612

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.907 AC: 61652 AN: 67992

Other (OTH) AF: 0.878 AC: 1854 AN: 2112

Alfa AF: 0.892 Hom.: 77030

Bravo AF: 0.860

Asia WGS AF: 0.704 AC: 2450 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 10, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.11
DANN	Benign	0.44
PhyloP100		-2.6
RBP_binding_hub_radar		0.85
RBP_regulation_power_radar		2.0
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: rs165824; hg19: chr22-19959366;