20-48922217-C-T

Position:

• chr20-48922217-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006420.3(ARFGEF2):​c.121+207C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00636 in 152,350 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0064 (6 hom., cov: 32)
• Consequence: ARFGEF2 NM_006420.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.65

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 20-48922217-C-T is Benign according to our data. Variant chr20-48922217-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1216921.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00636 (969/152350) while in subpopulation SAS AF= 0.023 (111/4828). AF 95% confidence interval is 0.0195. There are 6 homozygotes in gnomad4. There are 453 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARFGEF2	NM_006420.3	c.121+207C>T		intron_variant		ENST00000371917.5	NP_006411.2
ARFGEF2	NM_001410846.1	c.121+207C>T		intron_variant			NP_001397775.1
ARFGEF2	XM_047439832.1	c.-289+207C>T		intron_variant			XP_047295788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARFGEF2	ENST00000371917.5	c.121+207C>T		intron_variant		1	NM_006420.3	ENSP00000360985.4

Frequencies

GnomAD3 genomes AF: 0.00638 AC: 971 AN: 152232 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00154

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0234

Gnomad FIN AF: 0.00847

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00878

Gnomad OTH AF: 0.00764

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00636 AC: 969 AN: 152350 Hom.: 6 Cov.: 32 AF XY: 0.00608 AC XY: 453 AN XY: 74500

Gnomad4 AFR AF: 0.00154

Gnomad4 AMR AF: 0.00274

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0230

Gnomad4 FIN AF: 0.00847

Gnomad4 NFE AF: 0.00878

Gnomad4 OTH AF: 0.00756

Alfa AF: 0.00902 Hom.: 0

Bravo AF: 0.00533

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs144094432; hg19: chr20-47538754;