rs5993890

Variant names:

• chr22-19971306-G-A
• rs5993890
• NM_001670.3:c.2811C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-19971306-G-A
• chr22-19971306-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001670.3(ARVCF):​c.2811C>T​(p.Pro937Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0556 in 1,555,452 control chromosomes in the GnomAD database, including 2,960 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.075 (535 hom., cov: 34)
  • Exomes 𝑓: 0.054 (2425 hom.)
• Consequence: ARVCF NM_001670.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.23
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 22-19971306-G-A is Benign according to our data. Variant chr22-19971306-G-A is described in ClinVar as Benign. ClinVar VariationId is 1242019.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.23 with no splicing effect.
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARVCF	NM_001670.3	MANE Select	c.2811C>T	p.Pro937Pro	synonymous	Exon 19 of 20	NP_001661.1
	ARVCF	NM_001438684.1		c.2793C>T	p.Pro931Pro	synonymous	Exon 18 of 18	NP_001425613.1
	ARVCF	NM_001438685.1		c.2778C>T	p.Pro926Pro	synonymous	Exon 18 of 19	NP_001425614.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARVCF	ENST00000263207.8	TSL:1 MANE Select	c.2811C>T	p.Pro937Pro	synonymous	Exon 19 of 20	ENSP00000263207.3
	ARVCF	ENST00000406259.1	TSL:5	c.2793C>T	p.Pro931Pro	synonymous	Exon 16 of 16	ENSP00000385444.1
	ARVCF	ENST00000401994.5	TSL:5	c.2622C>T	p.Pro874Pro	synonymous	Exon 17 of 17	ENSP00000384341.1

Frequencies

GnomAD3 genomes AF: 0.0747 AC: 11369 AN: 152180 Hom.: 529 Cov.: 34

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.0766

Gnomad ASJ AF: 0.0844

Gnomad EAS AF: 0.0319

Gnomad SAS AF: 0.0894

Gnomad FIN AF: 0.0236

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0467

Gnomad OTH AF: 0.0827

GnomAD2 exomes AF: 0.0666 AC: 10683 AN: 160408 AF XY: 0.0688

Gnomad AFR exome AF: 0.144

Gnomad AMR exome AF: 0.0714

Gnomad ASJ exome AF: 0.0879

Gnomad EAS exome AF: 0.0369

Gnomad FIN exome AF: 0.0263

Gnomad NFE exome AF: 0.0525

Gnomad OTH exome AF: 0.0651

GnomAD4 exome AF: 0.0535 AC: 75120 AN: 1403154 Hom.: 2425 Cov.: 35 AF XY: 0.0548 AC XY: 37965 AN XY: 692500

African (AFR) AF: 0.140 AC: 4481 AN: 32052

American (AMR) AF: 0.0719 AC: 2626 AN: 36548

Ashkenazi Jewish (ASJ) AF: 0.0887 AC: 2235 AN: 25192

East Asian (EAS) AF: 0.0300 AC: 1096 AN: 36478

South Asian (SAS) AF: 0.0992 AC: 7907 AN: 79708

European-Finnish (FIN) AF: 0.0285 AC: 1376 AN: 48234

Middle Eastern (MID) AF: 0.0772 AC: 440 AN: 5702

European-Non Finnish (NFE) AF: 0.0473 AC: 51149 AN: 1081100

Other (OTH) AF: 0.0655 AC: 3810 AN: 58140

GnomAD4 genome AF: 0.0749 AC: 11410 AN: 152298 Hom.: 535 Cov.: 34 AF XY: 0.0740 AC XY: 5510 AN XY: 74484

African (AFR) AF: 0.136 AC: 5650 AN: 41540

American (AMR) AF: 0.0765 AC: 1171 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0844 AC: 293 AN: 3470

East Asian (EAS) AF: 0.0314 AC: 163 AN: 5186

South Asian (SAS) AF: 0.0894 AC: 432 AN: 4830

European-Finnish (FIN) AF: 0.0236 AC: 251 AN: 10628

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

European-Non Finnish (NFE) AF: 0.0467 AC: 3177 AN: 68016

Other (OTH) AF: 0.0823 AC: 174 AN: 2114

Alfa AF: 0.0485 Hom.: 121

Bravo AF: 0.0810

Asia WGS AF: 0.0790 AC: 275 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.58
CADD	Benign	0.73
DANN	Benign	0.94
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs5993890; hg19: chr22-19958829; COSMIC: COSV52889023; COSMIC: COSV52889023;