rs12885166

Variant names:

• chr14-92658937-G-T
• rs12885166
• NM_024832.5:c.2027-224G>T

Variant summary

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

The NM_024832.5(RIN3):​c.2027-224G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,090 control chromosomes in the GnomAD database, including 6,529 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 0.26 (6529 hom., cov: 32)
• Consequence: RIN3 NM_024832.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.633
• Publications: 8 publications found

Genes affected

RIN3 (HGNC:18751): (Ras and Rab interactor 3) Summary: This protein encoded by this gene is a member of the RIN family of Ras interaction-interference proteins, which are binding partners to the RAB5 small GTPases. The protein functions as a guanine nucleotide exchange for RAB5B and RAB31. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIN3	NM_024832.5	c.2027-224G>T		intron_variant	Intron 6 of 9	ENST00000216487.12	NP_079108.3
RIN3	NM_001319987.2	c.1802-224G>T		intron_variant	Intron 5 of 8		NP_001306916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIN3	ENST00000216487.12	c.2027-224G>T		intron_variant	Intron 6 of 9	1	NM_024832.5	ENSP00000216487.7

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39668 AN: 151972 Hom.: 6524 Cov.: 32

Gnomad AFR AF: 0.0689

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.261 AC: 39681 AN: 152090 Hom.: 6529 Cov.: 32 AF XY: 0.267 AC XY: 19880 AN XY: 74324

African (AFR) AF: 0.0687 AC: 2855 AN: 41532

American (AMR) AF: 0.313 AC: 4776 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1090 AN: 3470

East Asian (EAS) AF: 0.438 AC: 2263 AN: 5166

South Asian (SAS) AF: 0.243 AC: 1174 AN: 4824

European-Finnish (FIN) AF: 0.415 AC: 4380 AN: 10554

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22376 AN: 67952

Other (OTH) AF: 0.239 AC: 506 AN: 2114

Alfa AF: 0.301 Hom.: 11834

Bravo AF: 0.246

Asia WGS AF: 0.307 AC: 1070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.31
PhyloP100		0.63
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: rs12885166; hg19: chr14-93125282;