20-49017469-A-AT

Variant names:

• chr20-49017469-A-AT
• rs11086275
• NM_006420.3:c.4455-19dupT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.151

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARFGEF2	NM_006420.3	c.4455-19dupT		intron_variant	Intron 32 of 38	ENST00000371917.5	NP_006411.2
ARFGEF2	NM_001410846.1	c.4452-19dupT		intron_variant	Intron 32 of 38		NP_001397775.1
ARFGEF2	XM_047439832.1	c.3891-19dupT		intron_variant	Intron 30 of 36		XP_047295788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARFGEF2	ENST00000371917.5	c.4455-27_4455-26insT		intron_variant	Intron 32 of 38	1	NM_006420.3	ENSP00000360985.4

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37238 AN: 151588 Hom.: 5245 Cov.: 25

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

GnomAD3 exomes AF: 0.312 AC: 78149 AN: 250806 Hom.: 13430 AF XY: 0.309 AC XY: 41951 AN XY: 135582

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 SAS exome AF: 0.356

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.: 33 AF XY: 0.283 AC XY: 205589 AN XY: 726348

Gnomad4 AFR exome AF: 0.108

Gnomad4 AMR exome AF: 0.428

Gnomad4 ASJ exome AF: 0.269

Gnomad4 EAS exome AF: 0.450

Gnomad4 SAS exome AF: 0.348

Gnomad4 FIN exome AF: 0.268

Gnomad4 NFE exome AF: 0.269

Gnomad4 OTH exome AF: 0.284

GnomAD4 genome AF: 0.246 AC: 37254 AN: 151706 Hom.: 5250 Cov.: 25 AF XY: 0.254 AC XY: 18853 AN XY: 74104

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.274

Asia WGS AF: 0.372 AC: 1295 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs11086275; hg19: chr20-47634006;