rs12885166

chr14-92658937-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
RIN3	NM_024832.5	c.2027-224G>T		intron_variant		ENST00000216487.12
RIN3	NM_001319987.2	c.1802-224G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIN3	ENST00000216487.12	c.2027-224G>T		intron_variant		1	NM_024832.5	P2

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

Gnomad4 AFR AF: 0.0687

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.239

Alfa AF: 0.309 Hom.: 8817

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs12885166; hg19: chr14-93125282;