16-18793431-CT-C

Position:

• chr16-18793431-CT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015161.3(ARL6IP1):​c.494-62del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 602,714 control chromosomes in the GnomAD database, including 8,171 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (7186 hom., cov: 0)
  • Exomes 𝑓: 0.35 (985 hom.)
• Consequence: ARL6IP1 NM_015161.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.236

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 -10 ACMG points.

• BP6: Variant 16-18793431-CT-C is Benign according to our data. Variant chr16-18793431-CT-C is described in ClinVar as [Benign]. Clinvar id is 1262023.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARL6IP1	NM_015161.3	c.494-62del		intron_variant		ENST00000304414.12	NP_055976.1
ARL6IP1	NM_001313858.1	c.407-62del		intron_variant			NP_001300787.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARL6IP1	ENST00000304414.12	c.494-62del		intron_variant		1	NM_015161.3	ENSP00000306788	P1
ARL6IP1	ENST00000563861.5	c.*76-62del		intron_variant, NMD_transcript_variant		1		ENSP00000456596
ARL6IP1	ENST00000546206.6	c.407-62del		intron_variant		2		ENSP00000440048
ARL6IP1	ENST00000562819.5	c.149-62del		intron_variant		5		ENSP00000457372

Frequencies

GnomAD3 genomes AF: 0.324 AC: 45387 AN: 139966 Hom.: 7184 Cov.: 0

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.340

GnomAD4 exome AF: 0.355 AC: 164230 AN: 462764 Hom.: 985 AF XY: 0.354 AC XY: 85214 AN XY: 240606

Gnomad4 AFR exome AF: 0.331

Gnomad4 AMR exome AF: 0.333

Gnomad4 ASJ exome AF: 0.360

Gnomad4 EAS exome AF: 0.314

Gnomad4 SAS exome AF: 0.337

Gnomad4 FIN exome AF: 0.353

Gnomad4 NFE exome AF: 0.361

Gnomad4 OTH exome AF: 0.355

GnomAD4 genome AF: 0.324 AC: 45391 AN: 139950 Hom.: 7186 Cov.: 0 AF XY: 0.322 AC XY: 21681 AN XY: 67424

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.341

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

Mar 24, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs34143424; hg19: chr16-18804753;