chr12-69745893-T-G

Variant names:

• chr12-69745893-T-G
• rs11177823
• NM_022456.5:c.-26+6862T>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.-26+6862T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 152,010 control chromosomes in the GnomAD database, including 8,287 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 0.32 (8287 hom., cov: 32)
• Consequence: RAB3IP NM_022456.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022456.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB3IP	NM_022456.5	MANE Select	c.-26+6862T>G		intron	N/A	NP_071901.2
	RAB3IP	NM_175623.4		c.23+6024T>G		intron	N/A	NP_783322.1
	RAB3IP	NM_175625.4		c.23+6024T>G		intron	N/A	NP_783324.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB3IP	ENST00000247833.12	TSL:1 MANE Select	c.-26+6862T>G		intron	N/A	ENSP00000247833.7
	RAB3IP	ENST00000550536.5	TSL:1	c.23+6024T>G		intron	N/A	ENSP00000447300.1
	RAB3IP	ENST00000362025.9	TSL:1	c.23+6024T>G		intron	N/A	ENSP00000355381.5

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49013 AN: 151892 Hom.: 8284 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.322 AC: 49021 AN: 152010 Hom.: 8287 Cov.: 32 AF XY: 0.325 AC XY: 24142 AN XY: 74296

African (AFR) AF: 0.233 AC: 9676 AN: 41488

American (AMR) AF: 0.302 AC: 4614 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 967 AN: 3472

East Asian (EAS) AF: 0.249 AC: 1287 AN: 5160

South Asian (SAS) AF: 0.370 AC: 1786 AN: 4828

European-Finnish (FIN) AF: 0.406 AC: 4281 AN: 10544

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.372 AC: 25277 AN: 67926

Other (OTH) AF: 0.308 AC: 651 AN: 2114

Alfa AF: 0.349 Hom.: 19758

Bravo AF: 0.304

Asia WGS AF: 0.304 AC: 1055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.61
PhyloP100		0.083
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: rs11177823; hg19: chr12-70139673;