rs6549184

Positions:

• chr3-69101126-G-A
• chr3-69101126-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ARL6IP5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARL6IP5	NM_006407.4	c.177-713G>A		intron_variant		ENST00000273258.4	NP_006398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARL6IP5	ENST00000273258.4	c.177-713G>A		intron_variant		1	NM_006407.4	ENSP00000273258.3

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

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.0619

Gnomad4 ASJ AF: 0.0433

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.0660

Gnomad4 NFE AF: 0.0377

Gnomad4 OTH AF: 0.108

Alfa AF: 0.0536 Hom.: 257

Bravo AF: 0.130

Asia WGS AF: 0.222 AC: 773 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	1.9
DANN	Benign	0.26

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: rs6549184; hg19: chr3-69150277;