chr6-138210367-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020340.5(ARFGEF3):​c.351+326C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 151,898 control chromosomes in the GnomAD database, including 6,424 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 0.23 ( 6424 hom., cov: 32)

Consequence

ARFGEF3
NM_020340.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.910

Publications

1 publications found
Variant links:
Genes affected
ARFGEF3 (HGNC:21213): (ARFGEF family member 3) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in actin cytoskeleton organization. Predicted to be located in transport vesicle membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARFGEF3NM_020340.5 linkc.351+326C>T intron_variant Intron 4 of 33 ENST00000251691.5 NP_065073.3 Q5TH69
ARFGEF3XR_001743524.2 linkn.499+326C>T intron_variant Intron 4 of 34

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARFGEF3ENST00000251691.5 linkc.351+326C>T intron_variant Intron 4 of 33 1 NM_020340.5 ENSP00000251691.4 Q5TH69

Frequencies

GnomAD3 genomes
AF:
0.226
AC:
34341
AN:
151780
Hom.:
6386
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.504
Gnomad AMI
AF:
0.0208
Gnomad AMR
AF:
0.189
Gnomad ASJ
AF:
0.0831
Gnomad EAS
AF:
0.378
Gnomad SAS
AF:
0.126
Gnomad FIN
AF:
0.132
Gnomad MID
AF:
0.111
Gnomad NFE
AF:
0.0884
Gnomad OTH
AF:
0.186
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.227
AC:
34451
AN:
151898
Hom.:
6424
Cov.:
32
AF XY:
0.227
AC XY:
16816
AN XY:
74242
show subpopulations
African (AFR)
AF:
0.504
AC:
20844
AN:
41358
American (AMR)
AF:
0.190
AC:
2896
AN:
15250
Ashkenazi Jewish (ASJ)
AF:
0.0831
AC:
288
AN:
3464
East Asian (EAS)
AF:
0.379
AC:
1962
AN:
5178
South Asian (SAS)
AF:
0.126
AC:
606
AN:
4812
European-Finnish (FIN)
AF:
0.132
AC:
1393
AN:
10548
Middle Eastern (MID)
AF:
0.112
AC:
33
AN:
294
European-Non Finnish (NFE)
AF:
0.0884
AC:
6009
AN:
67968
Other (OTH)
AF:
0.190
AC:
401
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1106
2212
3319
4425
5531
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
320
640
960
1280
1600
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.176
Hom.:
1103
Bravo
AF:
0.247
Asia WGS
AF:
0.247
AC:
858
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
5.7
DANN
Benign
0.38
PhyloP100
0.91
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

Publications

Other links and lift over

dbSNP: rs4895514; hg19: chr6-138531504; API