rs17225638

Variant names:

• chr12-69800655-A-G
• rs17225638
• NM_022456.5:c.1017+318A>G

Variant summary

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

The NM_022456.5(RAB3IP):​c.1017+318A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,140 control chromosomes in the GnomAD database, including 1,181 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 0.11 (1181 hom., cov: 32)
• Consequence: RAB3IP NM_022456.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270
• Publications: 3 publications found

Genes affected

RAB3IP (HGNC:16508): (RAB3A interacting protein) Enables guanyl-nucleotide exchange factor activity and identical protein binding activity. Involved in cilium assembly; protein localization to organelle; and protein targeting to membrane. Located in centrosome; cytosol; and nucleus. [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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB3IP	NM_022456.5	c.1017+318A>G		intron_variant	Intron 7 of 10	ENST00000247833.12	NP_071901.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB3IP	ENST00000247833.12	c.1017+318A>G		intron_variant	Intron 7 of 10	1	NM_022456.5	ENSP00000247833.7

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16182 AN: 152022 Hom.: 1180 Cov.: 32

Gnomad AFR AF: 0.0305

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0367

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.106 AC: 16178 AN: 152140 Hom.: 1181 Cov.: 32 AF XY: 0.101 AC XY: 7543 AN XY: 74394

African (AFR) AF: 0.0305 AC: 1266 AN: 41536

American (AMR) AF: 0.110 AC: 1679 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 504 AN: 3464

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.0371 AC: 179 AN: 4820

European-Finnish (FIN) AF: 0.102 AC: 1076 AN: 10598

Middle Eastern (MID) AF: 0.161 AC: 47 AN: 292

European-Non Finnish (NFE) AF: 0.163 AC: 11091 AN: 67948

Other (OTH) AF: 0.118 AC: 248 AN: 2108

Alfa AF: 0.120 Hom.: 216

Bravo AF: 0.103

Asia WGS AF: 0.0260 AC: 91 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.43
PhyloP100		-0.27
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: rs17225638; hg19: chr12-70194435;