20-49018802-A-G

Variant names:

• chr20-49018802-A-G
• rs9631141
• NM_006420.3:c.4510-82A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006420.3(ARFGEF2):​c.4510-82A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0716 in 1,086,906 control chromosomes in the GnomAD database, including 3,591 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.099 (1010 hom., cov: 32)
  • Exomes 𝑓: 0.067 (2581 hom.)
• Consequence: ARFGEF2 NM_006420.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.54
• Publications: 4 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 20-49018802-A-G is Benign according to our data. Variant chr20-49018802-A-G is described in ClinVar as Benign. ClinVar VariationId is 670370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 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.4510-82A>G		intron	N/A	NP_006411.2	Q9Y6D5
	ARFGEF2	NM_001410846.1		c.4507-82A>G		intron	N/A	NP_001397775.1	A0A7P0T7Z2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARFGEF2	ENST00000371917.5	TSL:1 MANE Select	c.4510-82A>G		intron	N/A	ENSP00000360985.4	Q9Y6D5
	ARFGEF2	ENST00000679436.1		c.4507-82A>G		intron	N/A	ENSP00000504888.1	A0A7P0T7Z2
	ARFGEF2	ENST00000939861.1		c.4504-82A>G		intron	N/A	ENSP00000609920.1

Frequencies

GnomAD3 genomes AF: 0.0992 AC: 15090 AN: 152126 Hom.: 1010 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0545

Gnomad ASJ AF: 0.0948

Gnomad EAS AF: 0.0822

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0346

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0642

Gnomad OTH AF: 0.0932

GnomAD4 exome AF: 0.0671 AC: 62749 AN: 934662 Hom.: 2581 AF XY: 0.0690 AC XY: 33548 AN XY: 485984

African (AFR) AF: 0.192 AC: 4423 AN: 23068

American (AMR) AF: 0.0359 AC: 1513 AN: 42110

Ashkenazi Jewish (ASJ) AF: 0.0907 AC: 2030 AN: 22386

East Asian (EAS) AF: 0.0564 AC: 2065 AN: 36590

South Asian (SAS) AF: 0.112 AC: 8270 AN: 74134

European-Finnish (FIN) AF: 0.0355 AC: 1834 AN: 51674

Middle Eastern (MID) AF: 0.121 AC: 569 AN: 4706

European-Non Finnish (NFE) AF: 0.0611 AC: 38926 AN: 637146

Other (OTH) AF: 0.0728 AC: 3119 AN: 42848

GnomAD4 genome AF: 0.0992 AC: 15104 AN: 152244 Hom.: 1010 Cov.: 32 AF XY: 0.0961 AC XY: 7155 AN XY: 74444

African (AFR) AF: 0.194 AC: 8040 AN: 41496

American (AMR) AF: 0.0545 AC: 833 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0948 AC: 329 AN: 3472

East Asian (EAS) AF: 0.0824 AC: 428 AN: 5192

South Asian (SAS) AF: 0.103 AC: 495 AN: 4826

European-Finnish (FIN) AF: 0.0346 AC: 368 AN: 10626

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0642 AC: 4368 AN: 68016

Other (OTH) AF: 0.0941 AC: 199 AN: 2114

Alfa AF: 0.0792 Hom.: 134

Bravo AF: 0.104

Asia WGS AF: 0.0720 AC: 250 AN: 3478

ClinVar

ClinVar submissions

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	-0.87
CADD	Benign	0.0070
DANN	Benign	0.68
PhyloP100		-1.5
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: rs9631141; hg19: chr20-47635339; COSMIC: COSV64211328;