NM_006421.5:c.124+1157G>A

Variant names:

• chr8-67342007-C-T
• rs7813810
• NM_006421.5:c.124+1157G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

ARFGEF1 Gene-Disease associations (from GenCC):

• developmental delay, impaired speech, and behavioral abnormalities, with or without seizures

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Illumina, Labcorp Genetics (formerly Invitae)
• schizophrenia

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

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 = 0.84 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006421.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARFGEF1	NM_006421.5	MANE Select	c.124+1157G>A		intron	N/A	NP_006412.2	Q9Y6D6
	ARFGEF1	NM_001413194.1		c.124+1157G>A		intron	N/A	NP_001400123.1
	ARFGEF1	NM_001413184.1		c.124+1157G>A		intron	N/A	NP_001400113.1	Q9Y6D6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARFGEF1	ENST00000262215.8	TSL:1 MANE Select	c.124+1157G>A		intron	N/A	ENSP00000262215.3	Q9Y6D6
	ARFGEF1	ENST00000882639.1		c.124+1157G>A		intron	N/A	ENSP00000552698.1
	ARFGEF1	ENST00000938941.1		c.124+1157G>A		intron	N/A	ENSP00000609000.1

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

African (AFR) AF: 0.848 AC: 35181 AN: 41494

American (AMR) AF: 0.428 AC: 6532 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1520 AN: 3464

East Asian (EAS) AF: 0.391 AC: 2021 AN: 5174

South Asian (SAS) AF: 0.377 AC: 1817 AN: 4822

European-Finnish (FIN) AF: 0.400 AC: 4208 AN: 10520

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.373 AC: 25349 AN: 67954

Other (OTH) AF: 0.486 AC: 1023 AN: 2106

Alfa AF: 0.416 Hom.: 6739

Bravo AF: 0.530

Asia WGS AF: 0.393 AC: 1366 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.0
DANN	Benign	0.33
PhyloP100		-0.011
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: rs7813810; hg19: chr8-68254242;