Variant 16-18793415-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.29

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARL6IP1	NM_015161.3 linkuse as main transcript	c.494-45G>A		intron_variant		ENST00000304414.12	NP_055976.1
ARL6IP1	NM_001313858.1 linkuse as main transcript	c.407-45G>A		intron_variant			NP_001300787.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
ARL6IP1	ENST00000304414.12 linkuse as main transcript	c.494-45G>A	intron_variant	1	NM_015161.3	ENSP00000306788	P1	Q15041-1
ARL6IP1	ENST00000563861.5 linkuse as main transcript	c.*76-45G>A	intron_variant, NMD_transcript_variant	1		ENSP00000456596
ARL6IP1	ENST00000546206.6 linkuse as main transcript	c.407-45G>A	intron_variant	2		ENSP00000440048		Q15041-2
ARL6IP1	ENST00000562819.5 linkuse as main transcript	c.149-45G>A	intron_variant	5		ENSP00000457372

Frequencies

GnomAD3 genomes

AF:

0.388

AC:

58527

AN:

150694

Hom.:

11737

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.402

AC:

70147

AN:

174546

Hom.:

14141

AF XY:

0.406

AC XY:

39089

AN XY:

96350

show subpopulations

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 SAS exome

AF:

0.350

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.:

AF XY:

0.412

AC XY:

203659

AN XY:

494220

show subpopulations

Gnomad4 AFR exome

AF:

0.319

Gnomad4 AMR exome

AF:

0.315

Gnomad4 ASJ exome

AF:

0.463

Gnomad4 EAS exome

AF:

0.131

Gnomad4 SAS exome

AF:

0.335

Gnomad4 FIN exome

AF:

0.436

Gnomad4 NFE exome

AF:

0.439

Gnomad4 OTH exome

AF:

0.406

GnomAD4 genome

AF:

0.388

AC:

58560

AN:

150790

Hom.:

11742

Cov.:

AF XY:

0.382

AC XY:

28112

AN XY:

73504

show subpopulations

Gnomad4 AFR

AF:

0.329

Gnomad4 AMR

AF:

0.360

Gnomad4 ASJ

AF:

0.465

Gnomad4 EAS

AF:

0.109

Gnomad4 SAS

AF:

0.333

Gnomad4 FIN

AF:

0.421

Gnomad4 NFE

AF:

0.445

Gnomad4 OTH

AF:

0.391

Alfa

AF:

0.436

Hom.:

13502

Bravo

AF:

0.380

Asia WGS

AF:

0.274

AC:

954

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 24, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

7.1

DANN

Benign

0.54

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over