13-49630889-T-C

Position:

• chr13-49630889-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138450.6(ARL11):​c.442T>C​(p.Cys148Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 1,587,468 control chromosomes in the GnomAD database, including 186,259 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.37 (12444 hom., cov: 31)
  • Exomes 𝑓: 0.48 (173815 hom.)
• Consequence: ARL11 NM_138450.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0010447502).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARL11	NM_138450.6	c.442T>C	p.Cys148Arg	missense_variant	2/2	ENST00000282026.2	NP_612459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARL11	ENST00000282026.2	c.442T>C	p.Cys148Arg	missense_variant	2/2	1	NM_138450.6	ENSP00000282026.1
ARL11	ENST00000490932.1	n.159+790T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56036 AN: 151852 Hom.: 12433 Cov.: 31

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.400

GnomAD3 exomes AF: 0.391 AC: 93390 AN: 238702 Hom.: 20466 AF XY: 0.394 AC XY: 50874 AN XY: 129074

Gnomad AFR exome AF: 0.129

Gnomad AMR exome AF: 0.351

Gnomad ASJ exome AF: 0.428

Gnomad EAS exome AF: 0.183

Gnomad SAS exome AF: 0.247

Gnomad FIN exome AF: 0.405

Gnomad NFE exome AF: 0.507

Gnomad OTH exome AF: 0.432

GnomAD4 exome AF: 0.479 AC: 688274 AN: 1435498 Hom.: 173815 Cov.: 57 AF XY: 0.474 AC XY: 336245 AN XY: 709992

Gnomad4 AFR exome AF: 0.126

Gnomad4 AMR exome AF: 0.355

Gnomad4 ASJ exome AF: 0.430

Gnomad4 EAS exome AF: 0.183

Gnomad4 SAS exome AF: 0.254

Gnomad4 FIN exome AF: 0.418

Gnomad4 NFE exome AF: 0.529

Gnomad4 OTH exome AF: 0.448

GnomAD4 genome AF: 0.369 AC: 56047 AN: 151970 Hom.: 12444 Cov.: 31 AF XY: 0.359 AC XY: 26669 AN XY: 74262

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.416

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.520

Gnomad4 OTH AF: 0.403

Alfa AF: 0.456 Hom.: 19551

Bravo AF: 0.362

TwinsUK AF: 0.530 AC: 1964

ALSPAC AF: 0.538 AC: 2072

ESP6500AA AF: 0.146 AC: 643

ESP6500EA AF: 0.514 AC: 4418

ExAC AF: 0.383 AC: 46510

Asia WGS AF: 0.224 AC: 780 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.023
DANN	Benign	0.29
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.45	T
MetaRNN	Benign	0.0010	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.35	N
REVEL	Benign	0.19
Sift	Benign	0.33	T
Sift4G	Benign	0.52	T
Polyphen		0.0010	B
Vest4		0.0060
MPC		0.27
ClinPred		0.034	T
GERP RS		-11
Varity_R		0.14
gMVP		0.24

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: rs3803185; hg19: chr13-50205025; COSMIC: COSV56291045;