chr20-49023200-A-G

Variant names:

• chr20-49023200-A-G
• rs7270848
• NM_006420.3:c.4755+19A>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.4755+19A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 1,613,152 control chromosomes in the GnomAD database, including 84,582 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10753 hom., cov: 31)
  • Exomes 𝑓: 0.31 (73829 hom.)
• Consequence: ARFGEF2 NM_006420.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.740
• Publications: 14 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=-0.81).
• BP6: Variant 20-49023200-A-G is Benign according to our data. Variant chr20-49023200-A-G is described in ClinVar as Benign. ClinVar VariationId is 259980.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.523 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARFGEF2	NM_006420.3	MANE Select	c.4755+19A>G		intron	N/A	NP_006411.2
	ARFGEF2	NM_001410846.1		c.4752+19A>G		intron	N/A	NP_001397775.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARFGEF2	ENST00000371917.5	TSL:1 MANE Select	c.4755+19A>G		intron	N/A	ENSP00000360985.4
	ARFGEF2	ENST00000679436.1		c.4752+19A>G		intron	N/A	ENSP00000504888.1
	ARFGEF2	ENST00000939861.1		c.4749+19A>G		intron	N/A	ENSP00000609920.1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54850 AN: 151892 Hom.: 10732 Cov.: 31

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.307

GnomAD2 exomes AF: 0.297 AC: 74579 AN: 250748 AF XY: 0.295

Gnomad AFR exome AF: 0.525

Gnomad AMR exome AF: 0.249

Gnomad ASJ exome AF: 0.272

Gnomad EAS exome AF: 0.155

Gnomad FIN exome AF: 0.268

Gnomad NFE exome AF: 0.315

Gnomad OTH exome AF: 0.293

GnomAD4 exome AF: 0.314 AC: 459443 AN: 1461142 Hom.: 73829 Cov.: 39 AF XY: 0.312 AC XY: 226899 AN XY: 726878

African (AFR) AF: 0.524 AC: 17528 AN: 33466

American (AMR) AF: 0.250 AC: 11178 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 7105 AN: 26120

East Asian (EAS) AF: 0.203 AC: 8054 AN: 39682

South Asian (SAS) AF: 0.278 AC: 23968 AN: 86246

European-Finnish (FIN) AF: 0.272 AC: 14504 AN: 53304

Middle Eastern (MID) AF: 0.274 AC: 1576 AN: 5758

European-Non Finnish (NFE) AF: 0.321 AC: 356963 AN: 1111534

Other (OTH) AF: 0.308 AC: 18567 AN: 60358

GnomAD4 genome AF: 0.361 AC: 54921 AN: 152010 Hom.: 10753 Cov.: 31 AF XY: 0.353 AC XY: 26270 AN XY: 74330

African (AFR) AF: 0.529 AC: 21882 AN: 41400

American (AMR) AF: 0.263 AC: 4018 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 948 AN: 3468

East Asian (EAS) AF: 0.189 AC: 977 AN: 5174

South Asian (SAS) AF: 0.277 AC: 1334 AN: 4812

European-Finnish (FIN) AF: 0.269 AC: 2850 AN: 10582

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21741 AN: 67974

Other (OTH) AF: 0.311 AC: 657 AN: 2112

Alfa AF: 0.334 Hom.: 1984

Bravo AF: 0.362

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.38
DANN	Benign	0.50
PhyloP100		-0.74
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: rs7270848; hg19: chr20-47639737; COSMIC: COSV107456882;