chr16-18793089-T-C

Variant names:

• chr16-18793089-T-C
• rs11540998
• NM_015161.3:c.*163A>G

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.*163A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0966 in 547,234 control chromosomes in the GnomAD database, including 2,889 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.097 (767 hom., cov: 33)
  • Exomes 𝑓: 0.096 (2122 hom.)
• Consequence: ARL6IP1 NM_015161.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.22
• Publications: 12 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=-0.79).
• BP6: Variant 16-18793089-T-C is Benign according to our data. Variant chr16-18793089-T-C is described in ClinVar as Benign. ClinVar VariationId is 1231012.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.

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.*163A>G		3_prime_UTR	Exon 6 of 6	NP_055976.1	Q15041-1
	ARL6IP1	NM_001313858.1		c.*163A>G		3_prime_UTR	Exon 6 of 6	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.*163A>G		3_prime_UTR	Exon 6 of 6	ENSP00000306788.7	Q15041-1
	ENSG00000260342	ENST00000567078.2	TSL:3	c.493+1510A>G		intron	N/A	ENSP00000454746.2	H3BN98
	ARL6IP1	ENST00000563861.5	TSL:1	n.*357A>G		non_coding_transcript_exon	Exon 5 of 5	ENSP00000456596.1	H3BS91

Frequencies

GnomAD3 genomes AF: 0.0975 AC: 14836 AN: 152166 Hom.: 769 Cov.: 33

Gnomad AFR AF: 0.0843

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0781

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0885

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.0962 AC: 37999 AN: 394950 Hom.: 2122 Cov.: 4 AF XY: 0.0984 AC XY: 20756 AN XY: 210962

African (AFR) AF: 0.0869 AC: 856 AN: 9848

American (AMR) AF: 0.139 AC: 2371 AN: 17056

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 2062 AN: 11880

East Asian (EAS) AF: 0.0790 AC: 2167 AN: 27428

South Asian (SAS) AF: 0.134 AC: 4522 AN: 33624

European-Finnish (FIN) AF: 0.0715 AC: 2163 AN: 30268

Middle Eastern (MID) AF: 0.156 AC: 261 AN: 1674

European-Non Finnish (NFE) AF: 0.0879 AC: 21158 AN: 240594

Other (OTH) AF: 0.108 AC: 2439 AN: 22578

GnomAD4 genome AF: 0.0975 AC: 14846 AN: 152284 Hom.: 767 Cov.: 33 AF XY: 0.100 AC XY: 7475 AN XY: 74466

African (AFR) AF: 0.0843 AC: 3504 AN: 41558

American (AMR) AF: 0.149 AC: 2274 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 624 AN: 3470

East Asian (EAS) AF: 0.123 AC: 638 AN: 5192

South Asian (SAS) AF: 0.127 AC: 615 AN: 4826

European-Finnish (FIN) AF: 0.0781 AC: 828 AN: 10604

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.0885 AC: 6020 AN: 68024

Other (OTH) AF: 0.124 AC: 262 AN: 2116

Alfa AF: 0.0945 Hom.: 1042

Bravo AF: 0.100

Asia WGS AF: 0.126 AC: 438 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	-0.79
CADD	Benign	0.48
DANN	Benign	0.60
PhyloP100		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11540998; hg19: chr16-18804411;