chr16-18794382-A-G

Position:

• chr16-18794382-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015161.3(ARL6IP1):​c.493+217T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0976 in 152,302 control chromosomes in the GnomAD database, including 767 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.098 (767 hom., cov: 33)
• Consequence: ARL6IP1 NM_015161.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.26

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]

ENSG00000260342 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 16-18794382-A-G is Benign according to our data. Variant chr16-18794382-A-G is described in ClinVar as [Benign]. Clinvar id is 1293091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARL6IP1	NM_015161.3	c.493+217T>C		intron_variant		ENST00000304414.12	NP_055976.1
ARL6IP1	NM_001313858.1	c.406+217T>C		intron_variant			NP_001300787.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARL6IP1	ENST00000304414.12	c.493+217T>C		intron_variant		1	NM_015161.3	ENSP00000306788.7
ENSG00000260342	ENST00000567078.2	c.493+217T>C		intron_variant		3		ENSP00000454746.2

Frequencies

GnomAD3 genomes AF: 0.0976 AC: 14852 AN: 152184 Hom.: 769 Cov.: 33

Gnomad AFR AF: 0.0844

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0784

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.0884

Gnomad OTH AF: 0.121

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0976 AC: 14862 AN: 152302 Hom.: 767 Cov.: 33 AF XY: 0.100 AC XY: 7484 AN XY: 74484

Gnomad4 AFR AF: 0.0845

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.0784

Gnomad4 NFE AF: 0.0884

Gnomad4 OTH AF: 0.124

Alfa AF: 0.0248 Hom.: 9

Bravo AF: 0.100

Asia WGS AF: 0.126 AC: 438 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 19, 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	-0.85
CADD	Benign	5.9
DANN	Benign	0.69

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: rs78436134; hg19: chr16-18805704;