chr1-228094994-C-T

Variant names:

• chr1-228094994-C-T
• rs3768331
• NM_001658.4:c.-37-2084C>T

Variant summary

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

The NM_001658.4(ARF1):​c.-37-2084C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 151,938 control chromosomes in the GnomAD database, including 8,711 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 0.33 (8711 hom., cov: 31)
• Consequence: ARF1 NM_001658.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 10 publications found

Genes affected

ARF1 (HGNC:652): (ADP ribosylation factor 1) ADP-ribosylation factor 1 (ARF1) is a member of the human ARF gene family. The family members encode small guanine nucleotide-binding proteins that stimulate the ADP-ribosyltransferase activity of cholera toxin and play a role in vesicular trafficking as activators of phospholipase D. The gene products, including 6 ARF proteins and 11 ARF-like proteins, constitute a family of the RAS superfamily. The ARF proteins are categorized as class I (ARF1, ARF2 and ARF3), class II (ARF4 and ARF5) and class III (ARF6), and members of each class share a common gene organization. The ARF1 protein is localized to the Golgi apparatus and has a central role in intra-Golgi transport. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ARF1 Gene-Disease associations (from GenCC):

• periventricular nodular heterotopia 8

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• periventricular nodular heterotopia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001658.4. 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
	ARF1	NM_001658.4	MANE Select	c.-37-2084C>T		intron	N/A	NP_001649.1
	ARF1	NM_001024226.2		c.-37-2084C>T		intron	N/A	NP_001019397.1
	ARF1	NM_001024227.1		c.-37-2084C>T		intron	N/A	NP_001019398.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARF1	ENST00000272102.10	TSL:1 MANE Select	c.-37-2084C>T		intron	N/A	ENSP00000272102.5
	ARF1	ENST00000470558.5	TSL:2	c.-37-2084C>T		intron	N/A	ENSP00000514654.1
	ARF1	ENST00000478336.5	TSL:2	c.-37-2084C>T		intron	N/A	ENSP00000514657.1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49584 AN: 151818 Hom.: 8702 Cov.: 31

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.326 AC: 49606 AN: 151938 Hom.: 8711 Cov.: 31 AF XY: 0.329 AC XY: 24397 AN XY: 74236

African (AFR) AF: 0.187 AC: 7756 AN: 41446

American (AMR) AF: 0.369 AC: 5631 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1297 AN: 3468

East Asian (EAS) AF: 0.333 AC: 1716 AN: 5154

South Asian (SAS) AF: 0.509 AC: 2450 AN: 4818

European-Finnish (FIN) AF: 0.338 AC: 3562 AN: 10526

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.381 AC: 25911 AN: 67950

Other (OTH) AF: 0.356 AC: 754 AN: 2116

Alfa AF: 0.375 Hom.: 20111

Bravo AF: 0.323

Asia WGS AF: 0.437 AC: 1518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.46
PhyloP100		-1.1
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: rs3768331; hg19: chr1-228282695;