chr3-5146561-T-C

Variant names:

• chr3-5146561-T-C
• rs11918654
• NM_018184.3:c.124-23942T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018184.3(ARL8B):​c.124-23942T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 152,068 control chromosomes in the GnomAD database, including 13,737 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.39 (13737 hom., cov: 32)
• Consequence: ARL8B NM_018184.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 10 publications found

Genes affected

ARL8B (HGNC:25564): (ADP ribosylation factor like GTPase 8B) Enables guanyl ribonucleotide binding activity and tubulin binding activity. Involved in several processes, including calcium ion regulated lysosome exocytosis; lysosomal transport; and vesicle fusion. Located in cytolytic granule membrane; midbody; and spindle midzone. Colocalizes with lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000233912 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARL8B	NM_018184.3	c.124-23942T>C		intron_variant	Intron 1 of 6	ENST00000256496.8	NP_060654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARL8B	ENST00000256496.8	c.124-23942T>C		intron_variant	Intron 1 of 6	1	NM_018184.3	ENSP00000256496.3

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59920 AN: 151948 Hom.: 13693 Cov.: 32

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.355

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.395 AC: 60023 AN: 152068 Hom.: 13737 Cov.: 32 AF XY: 0.395 AC XY: 29383 AN XY: 74328

African (AFR) AF: 0.652 AC: 27025 AN: 41456

American (AMR) AF: 0.314 AC: 4810 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1034 AN: 3470

East Asian (EAS) AF: 0.306 AC: 1581 AN: 5168

South Asian (SAS) AF: 0.290 AC: 1398 AN: 4820

European-Finnish (FIN) AF: 0.357 AC: 3784 AN: 10586

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19209 AN: 67952

Other (OTH) AF: 0.359 AC: 757 AN: 2110

Alfa AF: 0.335 Hom.: 18005

Bravo AF: 0.407

Asia WGS AF: 0.332 AC: 1154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.5
DANN	Benign	0.43
PhyloP100		-1.5
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: rs11918654; hg19: chr3-5188246;