rs7813810

Positions:

• chr8-67342007-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006421.5(ARFGEF1):​c.124+1157G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 152,014 control chromosomes in the GnomAD database, including 23,467 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 0.51 (23467 hom., cov: 32)
• Consequence: ARFGEF1 NM_006421.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110

Genes affected

ARFGEF1 (HGNC:15772): (ADP ribosylation factor guanine nucleotide exchange factor 1) 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. It contains a Sec7 domain, which may be responsible for guanine-nucleotide exchange activity and also brefeldin A inhibition. [provided by RefSeq, Aug 2011]

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 = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARFGEF1	NM_006421.5	c.124+1157G>A		intron_variant		ENST00000262215.8	NP_006412.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARFGEF1	ENST00000262215.8	c.124+1157G>A		intron_variant		1	NM_006421.5	ENSP00000262215	P1
ARFGEF1	ENST00000519436.1	c.124+1157G>A		intron_variant		3		ENSP00000429002

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77986 AN: 151896 Hom.: 23417 Cov.: 32

Gnomad AFR AF: 0.848

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.514 AC: 78094 AN: 152014 Hom.: 23467 Cov.: 32 AF XY: 0.512 AC XY: 38025 AN XY: 74284

Gnomad4 AFR AF: 0.848

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.391

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.486

Alfa AF: 0.413 Hom.: 5832

Bravo AF: 0.530

Asia WGS AF: 0.393 AC: 1366 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.0
DANN	Benign	0.33

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: rs7813810; hg19: chr8-68254242;