2-152720525-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_152522.7(ARL6IP6):c.401-8A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00281 in 1,613,046 control chromosomes in the GnomAD database, including 136 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (67 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (69 hom.)
• Consequence: ARL6IP6 NM_152522.7 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0002774
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0720

Genes affected

ARL6IP6 (HGNC:24048): (ADP ribosylation factor like GTPase 6 interacting protein 6) Predicted to be located in nuclear inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 2-152720525-A-G is Benign according to our data. Variant chr2-152720525-A-G is described in ClinVar as [Benign]. Clinvar id is 775761.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARL6IP6	NM_152522.7	c.401-8A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000326446.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARL6IP6	ENST00000326446.10	c.401-8A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_152522.7	P1

Frequencies

GnomAD3 genomes AF: 0.0154 AC: 2336 AN: 152126 Hom.: 68 Cov.: 33

Gnomad AFR AF: 0.0538

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00537

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.00379 AC: 954 AN: 251402 Hom.: 28 AF XY: 0.00286 AC XY: 389 AN XY: 135892

Gnomad AFR exome AF: 0.0541

Gnomad AMR exome AF: 0.00168

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000704

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00151 AC: 2199 AN: 1460802 Hom.: 69 Cov.: 31 AF XY: 0.00126 AC XY: 919 AN XY: 726798

Gnomad4 AFR exome AF: 0.0553

Gnomad4 AMR exome AF: 0.00181

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000405

Gnomad4 OTH exome AF: 0.00333

GnomAD4 genome AF: 0.0154 AC: 2338 AN: 152244 Hom.: 67 Cov.: 33 AF XY: 0.0146 AC XY: 1086 AN XY: 74440

Gnomad4 AFR AF: 0.0537

Gnomad4 AMR AF: 0.00536

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00715 Hom.: 14

Bravo AF: 0.0170

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.0000546

EpiControl AF: 0.00

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

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	10
Dann	Benign	0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00028
dbscSNV1_RF	Benign	0.0080
SpliceAI score (max)		0.020		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: rs75855930; hg19: chr2-153577039;