rs2668622

Variant names:

• chr17-46274765-G-T
• rs2668622
• NM_001103154.2:c.*675C>A

Variant summary

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

The NM_001103154.2(ARL17B):​c.*675C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 150,430 control chromosomes in the GnomAD database, including 1,921 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 0.14 (1915 hom., cov: 36)
  • Exomes 𝑓: 0.14 (6 hom.)
• Consequence: ARL17B NM_001103154.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94
• Publications: 21 publications found

Genes affected

ARL17B (HGNC:32387): (ADP ribosylation factor like GTPase 17B) Predicted to enable GTP binding activity. Predicted to be involved in intracellular protein transport and vesicle-mediated transport. Predicted to be located in Golgi apparatus. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000305133 (HGNC:):

LRRC37A (HGNC:29069): (leucine rich repeat containing 37A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARL17B	NM_001103154.2	c.*675C>A		3_prime_UTR_variant	Exon 5 of 5		NP_001096624.1
LRRC37A	XM_047437205.1	c.102-25029G>T		intron_variant	Intron 1 of 13		XP_047293161.1
LOC124904014	XR_007065823.1	n.76+674G>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARL17B	ENST00000570618.6	c.*675C>A		3_prime_UTR_variant	Exon 5 of 5	2		ENSP00000459151.1
ENSG00000305133	ENST00000809003.1	n.304+674G>T		intron_variant	Intron 4 of 7

Frequencies

GnomAD3 genomes AF: 0.145 AC: 21705 AN: 149878 Hom.: 1917 Cov.: 36

Gnomad AFR AF: 0.0440

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.00157

Gnomad SAS AF: 0.0743

Gnomad FIN AF: 0.0677

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.144 AC: 66 AN: 458 Hom.: 6 Cov.: 0 AF XY: 0.161 AC XY: 47 AN XY: 292

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.0984 AC: 36 AN: 366

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.359 AC: 28 AN: 78

Other (OTH) AF: 0.125 AC: 1 AN: 8

GnomAD4 genome AF: 0.145 AC: 21693 AN: 149972 Hom.: 1915 Cov.: 36 AF XY: 0.136 AC XY: 9919 AN XY: 73150

African (AFR) AF: 0.0439 AC: 1787 AN: 40738

American (AMR) AF: 0.177 AC: 2676 AN: 15082

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 819 AN: 3456

East Asian (EAS) AF: 0.00157 AC: 8 AN: 5086

South Asian (SAS) AF: 0.0744 AC: 356 AN: 4784

European-Finnish (FIN) AF: 0.0677 AC: 678 AN: 10022

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.217 AC: 14653 AN: 67524

Other (OTH) AF: 0.182 AC: 380 AN: 2090

Alfa AF: 0.191 Hom.: 979

Bravo AF: 0.151

Asia WGS AF: 0.0310 AC: 111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	17
DANN	Benign	0.55
PhyloP100		1.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2668622; hg19: chr17-44352131;