6-138285115-T-G

Position:

• chr6-138285115-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ARFGEF3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARFGEF3	NM_020340.5	c.2462-831T>G		intron_variant		ENST00000251691.5	NP_065073.3
ARFGEF3	XM_047419108.1	c.1967-831T>G		intron_variant			XP_047275064.1
ARFGEF3	XR_001743524.2	n.2610-831T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARFGEF3	ENST00000251691.5	c.2462-831T>G		intron_variant		1	NM_020340.5	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

Gnomad4 AFR AF: 0.787

Gnomad4 AMR AF: 0.483

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.479

Alfa AF: 0.386 Hom.: 18371

Bravo AF: 0.515

Asia WGS AF: 0.579 AC: 2013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.3
DANN	Benign	0.42

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: rs203136; hg19: chr6-138606252; COSMIC: COSV52453652;