17-46275856-T-G

Variant names:

• chr17-46275856-T-G
• rs2732703
• NM_001103154.2:c.*22-438A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001103154.2(ARL17B):​c.*22-438A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0978 in 142,284 control chromosomes in the GnomAD database, including 1 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 0.098 (1 hom., cov: 36)
• Consequence: ARL17B NM_001103154.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• Publications: 31 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]

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

ENSG00000305133 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Variant has high frequency in the NFE (0.149) population. However there is too low homozygotes in high coverage region: (expected more than 339, got 1).
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001103154.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL17B	NM_001103154.2		c.*22-438A>C		intron	N/A	NP_001096624.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL17B	ENST00000570618.6	TSL:2	c.*22-438A>C		intron	N/A	ENSP00000459151.1	Q8IVW1-2
	ARL17B	ENST00000705759.1		n.377-438A>C		intron	N/A
	ENSG00000305133	ENST00000809003.1		n.305-1453T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0979 AC: 13921 AN: 142186 Hom.: 1 Cov.: 36

Gnomad AFR AF: 0.0319

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0488

Gnomad FIN AF: 0.0385

Gnomad MID AF: 0.164

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.0978 AC: 13909 AN: 142284 Hom.: 1 Cov.: 36 AF XY: 0.0912 AC XY: 6373 AN XY: 69872

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0318 AC: 1294 AN: 40734

American (AMR) AF: 0.121 AC: 1711 AN: 14138

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 535 AN: 3122

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5184

South Asian (SAS) AF: 0.0486 AC: 226 AN: 4646

European-Finnish (FIN) AF: 0.0385 AC: 389 AN: 10100

Middle Eastern (MID) AF: 0.162 AC: 44 AN: 272

European-Non Finnish (NFE) AF: 0.152 AC: 9305 AN: 61334

Other (OTH) AF: 0.122 AC: 235 AN: 1932

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.167 Hom.: 33

Asia WGS AF: 0.0290 AC: 102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Benign	0.80
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs2732703; hg19: chr17-44353222;