chr16-18793415-C-T

Variant names:

• chr16-18793415-C-T
• rs2650628
• NM_015161.3:c.494-45G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015161.3(ARL6IP1):​c.494-45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 1,107,842 control chromosomes in the GnomAD database, including 98,026 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (11742 hom., cov: 30)
  • Exomes 𝑓: 0.41 (86284 hom.)
• Consequence: ARL6IP1 NM_015161.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.29
• Publications: 11 publications found

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]

ARL6IP1 Gene-Disease associations (from GenCC):

• hereditary spastic paraplegia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hereditary spastic paraplegia 61

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000260342 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 16-18793415-C-T is Benign according to our data. Variant chr16-18793415-C-T is described in ClinVar as Benign. ClinVar VariationId is 1221048.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015161.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL6IP1	NM_015161.3	MANE Select	c.494-45G>A		intron	N/A	NP_055976.1	Q15041-1
	ARL6IP1	NM_001313858.1		c.407-45G>A		intron	N/A	NP_001300787.1	Q15041-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL6IP1	ENST00000304414.12	TSL:1 MANE Select	c.494-45G>A		intron	N/A	ENSP00000306788.7	Q15041-1
	ENSG00000260342	ENST00000567078.2	TSL:3	c.493+1184G>A		intron	N/A	ENSP00000454746.2	H3BN98
	ARL6IP1	ENST00000563861.5	TSL:1	n.*76-45G>A		intron	N/A	ENSP00000456596.1	H3BS91

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58527 AN: 150694 Hom.: 11737 Cov.: 30

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.392

GnomAD2 exomes AF: 0.402 AC: 70147 AN: 174546 AF XY: 0.406

Gnomad AFR exome AF: 0.347

Gnomad AMR exome AF: 0.325

Gnomad ASJ exome AF: 0.492

Gnomad EAS exome AF: 0.131

Gnomad FIN exome AF: 0.442

Gnomad NFE exome AF: 0.457

Gnomad OTH exome AF: 0.422

GnomAD4 exome AF: 0.413 AC: 395393 AN: 957052 Hom.: 86284 Cov.: 12 AF XY: 0.412 AC XY: 203659 AN XY: 494220

African (AFR) AF: 0.319 AC: 6653 AN: 20842

American (AMR) AF: 0.315 AC: 8659 AN: 27496

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 9269 AN: 19998

East Asian (EAS) AF: 0.131 AC: 4688 AN: 35746

South Asian (SAS) AF: 0.335 AC: 22467 AN: 67042

European-Finnish (FIN) AF: 0.436 AC: 22089 AN: 50624

Middle Eastern (MID) AF: 0.403 AC: 1317 AN: 3264

European-Non Finnish (NFE) AF: 0.439 AC: 302963 AN: 689490

Other (OTH) AF: 0.406 AC: 17288 AN: 42550

GnomAD4 genome AF: 0.388 AC: 58560 AN: 150790 Hom.: 11742 Cov.: 30 AF XY: 0.382 AC XY: 28112 AN XY: 73504

African (AFR) AF: 0.329 AC: 13532 AN: 41094

American (AMR) AF: 0.360 AC: 5465 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1615 AN: 3470

East Asian (EAS) AF: 0.109 AC: 560 AN: 5154

South Asian (SAS) AF: 0.333 AC: 1596 AN: 4796

European-Finnish (FIN) AF: 0.421 AC: 4224 AN: 10030

Middle Eastern (MID) AF: 0.397 AC: 115 AN: 290

European-Non Finnish (NFE) AF: 0.445 AC: 30138 AN: 67758

Other (OTH) AF: 0.391 AC: 818 AN: 2090

Alfa AF: 0.429 Hom.: 17326

Bravo AF: 0.380

Asia WGS AF: 0.274 AC: 954 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.1
DANN	Benign	0.54
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2650628; hg19: chr16-18804737; COSMIC: COSV58614448; COSMIC: COSV58614448;