chr20-48921863-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_006420.3(ARFGEF2):c.-27G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000634 in 1,508,868 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00051 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00065 ( 5 hom. )
Consequence
ARFGEF2
NM_006420.3 5_prime_UTR
NM_006420.3 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.75
Genes affected
ARFGEF2 (HGNC:15853): (ADP ribosylation factor guanine nucleotide exchange factor 2) ADP-ribosylation factors (ARFs) play an important role in intracellular vesicular trafficking. The protein encoded by this gene is involved in the activation of ARFs by accelerating replacement of bound GDP with GTP and is involved in Golgi transport. It contains a Sec7 domain, which may be responsible for its guanine-nucleotide exchange activity and also brefeldin A inhibition. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
Variant 20-48921863-G-A is Benign according to our data. Variant chr20-48921863-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 377496.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000514 (78/151622) while in subpopulation SAS AF= 0.00642 (31/4830). AF 95% confidence interval is 0.00465. There are 0 homozygotes in gnomad4. There are 32 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARFGEF2 | NM_006420.3 | c.-27G>A | 5_prime_UTR_variant | 1/39 | ENST00000371917.5 | ||
ARFGEF2 | NM_001410846.1 | c.-27G>A | 5_prime_UTR_variant | 1/39 | |||
ARFGEF2 | XM_047439832.1 | c.-436G>A | 5_prime_UTR_variant | 1/37 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARFGEF2 | ENST00000371917.5 | c.-27G>A | 5_prime_UTR_variant | 1/39 | 1 | NM_006420.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000515 AC: 78AN: 151512Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
78
AN:
151512
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00155 AC: 188AN: 121670Hom.: 3 AF XY: 0.00186 AC XY: 122AN XY: 65650
GnomAD3 exomes
AF:
AC:
188
AN:
121670
Hom.:
AF XY:
AC XY:
122
AN XY:
65650
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000648 AC: 879AN: 1357246Hom.: 5 Cov.: 31 AF XY: 0.000804 AC XY: 538AN XY: 669174
GnomAD4 exome
AF:
AC:
879
AN:
1357246
Hom.:
Cov.:
31
AF XY:
AC XY:
538
AN XY:
669174
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000514 AC: 78AN: 151622Hom.: 0 Cov.: 32 AF XY: 0.000432 AC XY: 32AN XY: 74152
GnomAD4 genome
?
AF:
AC:
78
AN:
151622
Hom.:
Cov.:
32
AF XY:
AC XY:
32
AN XY:
74152
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 19, 2015 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at