3-69104703-G-T

Variant names:

• chr3-69104703-G-T
• rs7038
• NM_006407.4:c.*67G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006407.4(ARL6IP5):​c.*67G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,560,864 control chromosomes in the GnomAD database, including 154,562 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 0.49 (19123 hom., cov: 30)
  • Exomes 𝑓: 0.43 (135439 hom.)
• Consequence: ARL6IP5 NM_006407.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94
• Publications: 14 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARL6IP5	NM_006407.4	c.*67G>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000273258.4	NP_006398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARL6IP5	ENST00000273258.4	c.*67G>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_006407.4	ENSP00000273258.3
ARL6IP5	ENST00000478935.1	c.196-135G>T		intron_variant	Intron 2 of 2	1		ENSP00000420138.1
ARL6IP5	ENST00000484921.1	n.*450G>T		downstream_gene_variant		5		ENSP00000419374.1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73868 AN: 151558 Hom.: 19084 Cov.: 30

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.464

GnomAD4 exome AF: 0.433 AC: 610416 AN: 1409186 Hom.: 135439 Cov.: 26 AF XY: 0.435 AC XY: 304598 AN XY: 700104

African (AFR) AF: 0.678 AC: 21511 AN: 31746

American (AMR) AF: 0.310 AC: 12535 AN: 40466

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 9347 AN: 24482

East Asian (EAS) AF: 0.614 AC: 23901 AN: 38898

South Asian (SAS) AF: 0.518 AC: 42823 AN: 82668

European-Finnish (FIN) AF: 0.339 AC: 17594 AN: 51974

Middle Eastern (MID) AF: 0.455 AC: 2542 AN: 5588

European-Non Finnish (NFE) AF: 0.422 AC: 453837 AN: 1075024

Other (OTH) AF: 0.451 AC: 26326 AN: 58340

GnomAD4 genome AF: 0.488 AC: 73955 AN: 151678 Hom.: 19123 Cov.: 30 AF XY: 0.485 AC XY: 35927 AN XY: 74088

African (AFR) AF: 0.662 AC: 27362 AN: 41334

American (AMR) AF: 0.376 AC: 5727 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1290 AN: 3464

East Asian (EAS) AF: 0.617 AC: 3179 AN: 5152

South Asian (SAS) AF: 0.523 AC: 2512 AN: 4804

European-Finnish (FIN) AF: 0.337 AC: 3537 AN: 10498

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28775 AN: 67890

Other (OTH) AF: 0.465 AC: 982 AN: 2114

Alfa AF: 0.445 Hom.: 51077

Bravo AF: 0.496

Asia WGS AF: 0.555 AC: 1929 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	14
DANN	Benign	0.92
PhyloP100		1.9
Mutation Taster		=97/3	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: rs7038; hg19: chr3-69153854; COSMIC: COSV56235037; COSMIC: COSV56235037;