rs12098599

Variant names:

• chr10-18677031-G-T
• rs12098599
• NM_178815.5:c.*1815G>T

Variant summary

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

The NM_178815.5(ARL5B):​c.*1815G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 151,964 control chromosomes in the GnomAD database, including 3,575 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 0.21 (3566 hom., cov: 32)
  • Exomes 𝑓: 0.19 (9 hom.)
• Consequence: ARL5B NM_178815.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.311
• Publications: 6 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARL5B	NM_178815.5	c.*1815G>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000377275.4	NP_848930.1
ARL5B	XM_005252400.2	c.*1815G>T		3_prime_UTR_variant	Exon 5 of 5		XP_005252457.1
ARL5B	XM_005252401.5	c.*1815G>T		3_prime_UTR_variant	Exon 6 of 6		XP_005252458.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARL5B	ENST00000377275.4	c.*1815G>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_178815.5	ENSP00000366487.3

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31406 AN: 151410 Hom.: 3561 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.199

GnomAD4 exome AF: 0.189 AC: 83 AN: 438 Hom.: 9 Cov.: 0 AF XY: 0.189 AC XY: 50 AN XY: 264

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.190 AC: 81 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.125 AC: 1 AN: 8

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.208 AC: 31447 AN: 151526 Hom.: 3566 Cov.: 32 AF XY: 0.212 AC XY: 15727 AN XY: 74042

African (AFR) AF: 0.239 AC: 9888 AN: 41334

American (AMR) AF: 0.290 AC: 4415 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 526 AN: 3462

East Asian (EAS) AF: 0.227 AC: 1172 AN: 5160

South Asian (SAS) AF: 0.311 AC: 1498 AN: 4820

European-Finnish (FIN) AF: 0.192 AC: 2010 AN: 10480

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.167 AC: 11341 AN: 67764

Other (OTH) AF: 0.197 AC: 415 AN: 2102

Alfa AF: 0.187 Hom.: 581

Bravo AF: 0.211

Asia WGS AF: 0.320 AC: 1113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.0
DANN	Benign	0.60
PhyloP100		0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
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: rs12098599; hg19: chr10-18965960; COSMIC: COSV66011154;