chr22-19975440-G-T

Variant names:

• chr22-19975440-G-T
• rs2518824
• NM_001670.3:c.1960+246C>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+246C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 152,034 control chromosomes in the GnomAD database, including 27,635 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 0.58 (27635 hom., cov: 33)
• Consequence: ARVCF NM_001670.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• Publications: 16 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=-0.8).
• 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.1960+246C>A		intron_variant	Intron 11 of 19	ENST00000263207.8	NP_001661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARVCF	ENST00000263207.8	c.1960+246C>A		intron_variant	Intron 11 of 19	1	NM_001670.3	ENSP00000263207.3

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87974 AN: 151914 Hom.: 27642 Cov.: 33

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.579 AC: 87968 AN: 152034 Hom.: 27635 Cov.: 33 AF XY: 0.578 AC XY: 42923 AN XY: 74304

African (AFR) AF: 0.328 AC: 13597 AN: 41444

American (AMR) AF: 0.558 AC: 8532 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2145 AN: 3470

East Asian (EAS) AF: 0.501 AC: 2576 AN: 5140

South Asian (SAS) AF: 0.588 AC: 2839 AN: 4826

European-Finnish (FIN) AF: 0.711 AC: 7527 AN: 10586

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

European-Non Finnish (NFE) AF: 0.715 AC: 48567 AN: 67964

Other (OTH) AF: 0.600 AC: 1265 AN: 2108

Alfa AF: 0.676 Hom.: 49913

Bravo AF: 0.555

Asia WGS AF: 0.541 AC: 1882 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.6
DANN	Benign	0.78
PhyloP100		-0.018
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2518824; hg19: chr22-19962963;