6-138285115-T-G

Variant names:

• chr6-138285115-T-G
• rs203136
• NM_020340.5:c.2462-831T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020340.5(ARFGEF3):​c.2462-831T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 152,070 control chromosomes in the GnomAD database, including 21,052 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (21052 hom., cov: 32)
• Consequence: ARFGEF3 NM_020340.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147
• Publications: 16 publications found

Genes affected

ARFGEF3 (HGNC:21213): (ARFGEF family member 3) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in actin cytoskeleton organization. Predicted to be located in transport vesicle membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020340.5. 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
	ARFGEF3	NM_020340.5	MANE Select	c.2462-831T>G		intron	N/A	NP_065073.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARFGEF3	ENST00000251691.5	TSL:1 MANE Select	c.2462-831T>G		intron	N/A	ENSP00000251691.4

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74362 AN: 151950 Hom.: 21010 Cov.: 32

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.490 AC: 74460 AN: 152070 Hom.: 21052 Cov.: 32 AF XY: 0.487 AC XY: 36214 AN XY: 74346

African (AFR) AF: 0.787 AC: 32641 AN: 41490

American (AMR) AF: 0.483 AC: 7378 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1333 AN: 3468

East Asian (EAS) AF: 0.405 AC: 2096 AN: 5176

South Asian (SAS) AF: 0.567 AC: 2729 AN: 4810

European-Finnish (FIN) AF: 0.269 AC: 2846 AN: 10578

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.354 AC: 24048 AN: 67958

Other (OTH) AF: 0.479 AC: 1011 AN: 2110

Alfa AF: 0.394 Hom.: 26439

Bravo AF: 0.515

Asia WGS AF: 0.579 AC: 2013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.3
DANN	Benign	0.42
PhyloP100		-0.15
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: rs203136; hg19: chr6-138606252; COSMIC: COSV52453652;