rs887204

Variant names:

• chr22-19979545-G-A
• rs887204
• NM_001670.3:c.1396+198C>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.1396+198C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 817,398 control chromosomes in the GnomAD database, including 182,810 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (27556 hom., cov: 35)
  • Exomes 𝑓: 0.68 (155254 hom.)
• Consequence: ARVCF NM_001670.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.341
• Publications: 10 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 22-19979545-G-A is Benign according to our data. Variant chr22-19979545-G-A is described in ClinVar as Benign. ClinVar VariationId is 1223805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARVCF	NM_001670.3	c.1396+198C>T		intron_variant	Intron 6 of 19	ENST00000263207.8	NP_001661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARVCF	ENST00000263207.8	c.1396+198C>T		intron_variant	Intron 6 of 19	1	NM_001670.3	ENSP00000263207.3

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87807 AN: 152026 Hom.: 27563 Cov.: 35

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.602

GnomAD4 exome AF: 0.677 AC: 450177 AN: 665254 Hom.: 155254 AF XY: 0.673 AC XY: 226691 AN XY: 336826

African (AFR) AF: 0.322 AC: 5236 AN: 16262

American (AMR) AF: 0.543 AC: 9763 AN: 17974

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 8998 AN: 14780

East Asian (EAS) AF: 0.525 AC: 16355 AN: 31166

South Asian (SAS) AF: 0.571 AC: 27339 AN: 47868

European-Finnish (FIN) AF: 0.711 AC: 21012 AN: 29532

Middle Eastern (MID) AF: 0.649 AC: 1596 AN: 2460

European-Non Finnish (NFE) AF: 0.717 AC: 338570 AN: 472364

Other (OTH) AF: 0.649 AC: 21308 AN: 32848

GnomAD4 genome AF: 0.577 AC: 87802 AN: 152144 Hom.: 27556 Cov.: 35 AF XY: 0.576 AC XY: 42821 AN XY: 74358

African (AFR) AF: 0.325 AC: 13472 AN: 41488

American (AMR) AF: 0.552 AC: 8448 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2145 AN: 3472

East Asian (EAS) AF: 0.505 AC: 2605 AN: 5160

South Asian (SAS) AF: 0.587 AC: 2829 AN: 4820

European-Finnish (FIN) AF: 0.710 AC: 7527 AN: 10604

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.715 AC: 48583 AN: 67988

Other (OTH) AF: 0.601 AC: 1271 AN: 2114

Alfa AF: 0.649 Hom.: 76579

Bravo AF: 0.554

Asia WGS AF: 0.542 AC: 1884 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	0.40
DANN	Benign	0.40
PhyloP100		-0.34
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: rs887204; hg19: chr22-19967068;