16-18793493-G-A

Position:

• chr16-18793493-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015161.3(ARL6IP1):​c.494-123C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0988 in 553,562 control chromosomes in the GnomAD database, including 3,019 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (765 hom., cov: 31)
  • Exomes 𝑓: 0.098 (2254 hom.)
• Consequence: ARL6IP1 NM_015161.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.47

Genes affected

ARL6IP1 (HGNC:697): (ADP ribosylation factor like GTPase 6 interacting protein 1) This gene belongs to the ARL6ip family and encodes a transmembrane protein that is predominantly localized to intracytoplasmic membranes. It is highly expressed in early myeloid progenitor cells and thought to be involved in protein transport, membrane trafficking, or cell signaling during hematopoietic maturation. Mutations in this gene are associated with spastic paraplegia 61 (SPG61). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 16-18793493-G-A is Benign according to our data. Variant chr16-18793493-G-A is described in ClinVar as [Benign]. Clinvar id is 1223035.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARL6IP1	NM_015161.3	c.494-123C>T		intron_variant		ENST00000304414.12	NP_055976.1
ARL6IP1	NM_001313858.1	c.407-123C>T		intron_variant			NP_001300787.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARL6IP1	ENST00000304414.12	c.494-123C>T		intron_variant		1	NM_015161.3	ENSP00000306788	P1
ARL6IP1	ENST00000563861.5	c.*76-123C>T		intron_variant, NMD_transcript_variant		1		ENSP00000456596
ARL6IP1	ENST00000546206.6	c.407-123C>T		intron_variant		2		ENSP00000440048
ARL6IP1	ENST00000562819.5	c.149-123C>T		intron_variant		5		ENSP00000457372

Frequencies

GnomAD3 genomes AF: 0.102 AC: 14756 AN: 144948 Hom.: 767 Cov.: 31

Gnomad AFR AF: 0.0895

Gnomad AMI AF: 0.0342

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0853

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.0908

Gnomad OTH AF: 0.127

GnomAD4 exome AF: 0.0978 AC: 39953 AN: 408516 Hom.: 2254 AF XY: 0.101 AC XY: 22034 AN XY: 218260

Gnomad4 AFR exome AF: 0.0885

Gnomad4 AMR exome AF: 0.145

Gnomad4 ASJ exome AF: 0.172

Gnomad4 EAS exome AF: 0.0833

Gnomad4 SAS exome AF: 0.142

Gnomad4 FIN exome AF: 0.0712

Gnomad4 NFE exome AF: 0.0883

Gnomad4 OTH exome AF: 0.107

GnomAD4 genome AF: 0.102 AC: 14764 AN: 145046 Hom.: 765 Cov.: 31 AF XY: 0.105 AC XY: 7418 AN XY: 70472

Gnomad4 AFR AF: 0.0895

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.0853

Gnomad4 NFE AF: 0.0908

Gnomad4 OTH AF: 0.129

Alfa AF: 0.0865 Hom.: 71

Bravo AF: 0.101

Asia WGS AF: 0.126 AC: 440 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.88
DANN	Benign	0.45

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: rs12919495; hg19: chr16-18804815;