Genetic Variant ARFGEF2:c.4455-19dupT (chr20-49017469-A-AT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_006420.3(ARFGEF2):c.4455-19dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 1,611,852 control chromosomes in the GnomAD database, including 64,654 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.25 ( 5250 hom., cov: 25)

Exomes 𝑓: 0.28 ( 59404 hom. )

Consequence

ARFGEF2
NM_006420.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.151

Publications

4 publications found

Variant links:

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]

ARFGEF2 links:

CSE1L-DT (HGNC:51232): (CSE1L divergent transcript)

CSE1L-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 20-49017469-A-AT is Benign according to our data. Variant chr20-49017469-A-AT is described in ClinVar as Benign. ClinVar VariationId is 1223977.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006420.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARFGEF2	NM_006420.3	MANE Select	c.4455-19dupT		intron	N/A	NP_006411.2	Q9Y6D5
	ARFGEF2	NM_001410846.1		c.4452-19dupT		intron	N/A	NP_001397775.1	A0A7P0T7Z2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARFGEF2	ENST00000371917.5	TSL:1 MANE Select	c.4455-19dupT	intron	N/A	ENSP00000360985.4	Q9Y6D5
ARFGEF2	ENST00000679436.1		c.4452-19dupT	intron	N/A	ENSP00000504888.1	A0A7P0T7Z2
ARFGEF2	ENST00000939861.1		c.4449-19dupT	intron	N/A	ENSP00000609920.1

Frequencies

GnomAD3 genomes

AF:

0.246

AC:

37238

AN:

151588

Hom.:

5245

Cov.:

show subpopulations

Gnomad AFR

AF:

0.114

Gnomad AMI

AF:

0.154

Gnomad AMR

AF:

0.370

Gnomad ASJ

AF:

0.250

Gnomad EAS

AF:

0.473

Gnomad SAS

AF:

0.352

Gnomad FIN

AF:

0.261

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.271

Gnomad OTH

AF:

0.275

GnomAD2 exomes

AF:

0.312

AC:

78149

AN:

250806

AF XY:

0.309

show subpopulations

Gnomad AFR exome

AF:

0.113

Gnomad AMR exome

AF:

0.442

Gnomad ASJ exome

AF:

0.272

Gnomad EAS exome

AF:

0.488

Gnomad FIN exome

AF:

0.266

Gnomad NFE exome

AF:

0.273

Gnomad OTH exome

AF:

0.288

GnomAD4 exome

AF:

0.280

AC:

408939

AN:

1460146

Hom.:

59404

Cov.:

AF XY:

0.283

AC XY:

205589

AN XY:

726348

show subpopulations

African (AFR)

AF:

0.108

AC:

3618

AN:

33462

American (AMR)

AF:

0.428

AC:

19103

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.269

AC:

7021

AN:

26116

East Asian (EAS)

AF:

0.450

AC:

17836

AN:

39640

South Asian (SAS)

AF:

0.348

AC:

29979

AN:

86080

European-Finnish (FIN)

AF:

0.268

AC:

14251

AN:

53214

Middle Eastern (MID)

AF:

0.256

AC:

1476

AN:

5762

European-Non Finnish (NFE)

AF:

0.269

AC:

298548

AN:

1110876

Other (OTH)

AF:

0.284

AC:

17107

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

15707

31414

47121

62828

78535

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10162

20324

30486

40648

50810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.246

AC:

37254

AN:

151706

Hom.:

5250

Cov.:

AF XY:

0.254

AC XY:

18853

AN XY:

74104

show subpopulations

African (AFR)

AF:

0.115

AC:

4739

AN:

41388

American (AMR)

AF:

0.371

AC:

5636

AN:

15206

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

865

AN:

3466

East Asian (EAS)

AF:

0.473

AC:

2431

AN:

5144

South Asian (SAS)

AF:

0.350

AC:

1680

AN:

4796

European-Finnish (FIN)

AF:

0.261

AC:

2744

AN:

10498

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.271

AC:

18373

AN:

67888

Other (OTH)

AF:

0.274

AC:

580

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1322

2644

3966

5288

6610

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

404

808

1212

1616

2020

<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:

0.154

Hom.:

454

Asia WGS

AF:

0.372

AC:

1295

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

20-49017469-AT-ATT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over