3-69101126-G-A

Variant names:

• chr3-69101126-G-A
• rs6549184
• NM_006407.4:c.177-713G>A

Variant summary

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

The NM_006407.4(ARL6IP5):​c.177-713G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 151,804 control chromosomes in the GnomAD database, including 2,045 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 0.12 (2045 hom., cov: 31)
• Consequence: ARL6IP5 NM_006407.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200
• Publications: 5 publications found

Genes affected

ARL6IP5 (HGNC:16937): (ADP ribosylation factor like GTPase 6 interacting protein 5) Expression of this gene is affected by vitamin A. The encoded protein of this gene may be associated with the cytoskeleton. A similar protein in rats may play a role in the regulation of cell differentiation. The rat protein binds and inhibits the cell membrane glutamate transporter EAAC1. The expression of the rat gene is upregulated by retinoic acid, which results in a specific reduction in EAAC1-mediated glutamate transport. [provided by RefSeq, Jul 2008]

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 (EAS) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006407.4. 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
	ARL6IP5	NM_006407.4	MANE Select	c.177-713G>A		intron	N/A	NP_006398.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL6IP5	ENST00000273258.4	TSL:1 MANE Select	c.177-713G>A		intron	N/A	ENSP00000273258.3
	ARL6IP5	ENST00000478935.1	TSL:1	c.177-713G>A		intron	N/A	ENSP00000420138.1
	ARL6IP5	ENST00000470936.1	TSL:2	n.189-713G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18535 AN: 151686 Hom.: 2030 Cov.: 31

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0621

Gnomad ASJ AF: 0.0433

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.0660

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.0377

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.122 AC: 18590 AN: 151804 Hom.: 2045 Cov.: 31 AF XY: 0.126 AC XY: 9337 AN XY: 74174

African (AFR) AF: 0.274 AC: 11327 AN: 41334

American (AMR) AF: 0.0619 AC: 944 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0433 AC: 150 AN: 3466

East Asian (EAS) AF: 0.360 AC: 1849 AN: 5132

South Asian (SAS) AF: 0.167 AC: 804 AN: 4808

European-Finnish (FIN) AF: 0.0660 AC: 695 AN: 10530

Middle Eastern (MID) AF: 0.0890 AC: 26 AN: 292

European-Non Finnish (NFE) AF: 0.0377 AC: 2565 AN: 67974

Other (OTH) AF: 0.108 AC: 228 AN: 2110

Alfa AF: 0.0548 Hom.: 300

Bravo AF: 0.130

Asia WGS AF: 0.222 AC: 773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.26
PhyloP100		0.020
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: rs6549184; hg19: chr3-69150277;