rs12767046

Positions:

• chr10-18674858-G-T

Variant summary

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

The NM_178815.5(ARL5B):​c.492-310G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 151,990 control chromosomes in the GnomAD database, including 2,858 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 0.18 (2858 hom., cov: 32)
• Consequence: ARL5B NM_178815.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.87

Genes affected

ARL5B (HGNC:23052): (ADP ribosylation factor like GTPase 5B) ARL5B (ARL8) belongs to a family of proteins that are structurally similar to ADP-ribosylation factors (ARFs; see MIM 103180). ARLs and ARFs are part of the RAS superfamily of regulatory GTPases.[supplied by OMIM, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARL5B	NM_178815.5	c.492-310G>T		intron_variant		ENST00000377275.4	NP_848930.1
ARL5B	XM_005252400.2	c.408-310G>T		intron_variant			XP_005252457.1
ARL5B	XM_005252401.5	c.381-310G>T		intron_variant			XP_005252458.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARL5B	ENST00000377275.4	c.492-310G>T		intron_variant		1	NM_178815.5	ENSP00000366487	P1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27951 AN: 151872 Hom.: 2857 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.184 AC: 27980 AN: 151990 Hom.: 2858 Cov.: 32 AF XY: 0.191 AC XY: 14169 AN XY: 74280

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.170

Alfa AF: 0.174 Hom.: 415

Bravo AF: 0.185

Asia WGS AF: 0.312 AC: 1086 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.020
DANN	Benign	0.57

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: rs12767046; hg19: chr10-18963787;