Variant 13-49630893-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_138450.6(ARL11):c.446G>A(p.Trp149*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0095 in 1,588,784 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0080 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0097 ( 75 hom. )

Consequence

ARL11
NM_138450.6 stop_gained

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.18

Variant links:

Genes affected

ARL11 (HGNC:24046): (ADP ribosylation factor like GTPase 11) This gene encodes a tumor suppressor related to the ADP-ribosylation factor (ARF) family of proteins. The encoded protein may play a role in apoptosis in a caspase-dependent manner. Polymorphisms in this gene have been associated with some familial cancers. [provided by RefSeq, May 2010]

ARL11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 13-49630893-G-A is Benign according to our data. Variant chr13-49630893-G-A is described in ClinVar as [Benign]. Clinvar id is 769852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00966 (13880/1436498) while in subpopulation MID AF= 0.0225 (127/5654). AF 95% confidence interval is 0.0193. There are 75 homozygotes in gnomad4_exome. There are 6970 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARL11	NM_138450.6 link	c.446G>A	p.Trp149*	stop_gained	2/2	ENST00000282026.2	NP_612459.1	Q969Q4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARL11	ENST00000282026.2 link	c.446G>A	p.Trp149*	stop_gained	2/2	1	NM_138450.6	ENSP00000282026.1		Q969Q4
ARL11	ENST00000490932.1 link	n.159+794G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00798

AC:

1214

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.00975

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00848

Gnomad FIN

AF:

0.00631

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0112

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00967

AC:

2300

AN:

237950

Hom.:

AF XY:

0.0102

AC XY:

1308

AN XY:

128726

show subpopulations

Gnomad AFR exome

AF:

0.00131

Gnomad AMR exome

AF:

0.00702

Gnomad ASJ exome

AF:

0.0236

Gnomad EAS exome

AF:

0.0000553

Gnomad SAS exome

AF:

0.0102

Gnomad FIN exome

AF:

0.00681

Gnomad NFE exome

AF:

0.0123

Gnomad OTH exome

AF:

0.0148

GnomAD4 exome

AF:

0.00966

AC:

13880

AN:

1436498

Hom.:

Cov.:

AF XY:

0.00981

AC XY:

6970

AN XY:

710730

show subpopulations

Gnomad4 AFR exome

AF:

0.00174

Gnomad4 AMR exome

AF:

0.00785

Gnomad4 ASJ exome

AF:

0.0214

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0107

Gnomad4 FIN exome

AF:

0.00621

Gnomad4 NFE exome

AF:

0.0101

Gnomad4 OTH exome

AF:

0.00971

GnomAD4 genome

AF:

0.00796

AC:

1212

AN:

152286

Hom.:

Cov.:

AF XY:

0.00794

AC XY:

591

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00156

Gnomad4 AMR

AF:

0.00974

Gnomad4 ASJ

AF:

0.0187

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00828

Gnomad4 FIN

AF:

0.00631

Gnomad4 NFE

AF:

0.0112

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00989

Hom.:

Bravo

AF:

0.00816

TwinsUK

AF:

0.0102

AC:

ALSPAC

AF:

0.0114

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.0116

AC:

100

ExAC

AF:

0.00974

AC:

1182

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.63

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.96

Vest4

0.26

GERP RS

5.3

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over