10-18661626-T-C

Variant summary

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

The NM_178815.5(ARL5B):c.46+1943T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 152,164 control chromosomes in the GnomAD database, including 47,307 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 0.79 (47307 hom., cov: 33)
• Consequence: ARL5B NM_178815.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0780

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 (EAS) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARL5B	NM_178815.5	c.46+1943T>C		intron_variant		ENST00000377275.4
ARL5B	XM_005252400.2	c.46+1943T>C		intron_variant
ARL5B	XM_005252401.5	c.-66+1734T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARL5B	ENST00000377275.4	c.46+1943T>C		intron_variant		1	NM_178815.5	P1

Frequencies

GnomAD3 genomes AF: 0.788 AC: 119818 AN: 152046 Hom.: 47294 Cov.: 33

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.979

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.777

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

GnomAD4 genome AF: 0.788 AC: 119872 AN: 152164 Hom.: 47307 Cov.: 33 AF XY: 0.787 AC XY: 58518 AN XY: 74396

Gnomad4 AFR AF: 0.763

Gnomad4 AMR AF: 0.763

Gnomad4 ASJ AF: 0.742

Gnomad4 EAS AF: 0.979

Gnomad4 SAS AF: 0.810

Gnomad4 FIN AF: 0.780

Gnomad4 NFE AF: 0.795

Gnomad4 OTH AF: 0.769

Alfa AF: 0.792 Hom.: 103295

Bravo AF: 0.783

Asia WGS AF: 0.858 AC: 2980 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	4.1
Dann	Benign	0.53

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: rs10829156; hg19: chr10-18950555;