chr2-152720525-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

2
Splicing: ADA: 0.0002774
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0720
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
ARL6IP6NM_152522.7 linkuse as main transcriptc.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
ARL6IP6ENST00000326446.10 linkuse as main transcriptc.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
show subpopulations
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
show subpopulations
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
show subpopulations
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
show subpopulations
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
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 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

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

Other links and lift over

dbSNP: rs75855930; hg19: chr2-153577039; API