chr6-138210367-C-T

Variant names:

• chr6-138210367-C-T
• rs4895514
• NM_020340.5:c.351+326C>T

Variant summary

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

The NM_020340.5(ARFGEF3):​c.351+326C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 151,898 control chromosomes in the GnomAD database, including 6,424 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 0.23 (6424 hom., cov: 32)
• Consequence: ARFGEF3 NM_020340.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.910
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARFGEF3	NM_020340.5	c.351+326C>T		intron_variant	Intron 4 of 33	ENST00000251691.5	NP_065073.3
ARFGEF3	XR_001743524.2	n.499+326C>T		intron_variant	Intron 4 of 34

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARFGEF3	ENST00000251691.5	c.351+326C>T		intron_variant	Intron 4 of 33	1	NM_020340.5	ENSP00000251691.4

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34341 AN: 151780 Hom.: 6386 Cov.: 32

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.0831

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0884

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.227 AC: 34451 AN: 151898 Hom.: 6424 Cov.: 32 AF XY: 0.227 AC XY: 16816 AN XY: 74242

African (AFR) AF: 0.504 AC: 20844 AN: 41358

American (AMR) AF: 0.190 AC: 2896 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.0831 AC: 288 AN: 3464

East Asian (EAS) AF: 0.379 AC: 1962 AN: 5178

South Asian (SAS) AF: 0.126 AC: 606 AN: 4812

European-Finnish (FIN) AF: 0.132 AC: 1393 AN: 10548

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0884 AC: 6009 AN: 67968

Other (OTH) AF: 0.190 AC: 401 AN: 2114

Alfa AF: 0.176 Hom.: 1103

Bravo AF: 0.247

Asia WGS AF: 0.247 AC: 858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.7
DANN	Benign	0.38
PhyloP100		0.91
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: rs4895514; hg19: chr6-138531504;