NM_024832.5:c.533-2517G>C

Variant names:

• chr14-92649065-G-C
• rs754388
• NM_024832.5:c.533-2517G>C

Variant summary

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

The NM_024832.5(RIN3):​c.533-2517G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.842 in 152,168 control chromosomes in the GnomAD database, including 54,081 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 0.84 (54081 hom., cov: 31)
• Consequence: RIN3 NM_024832.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 42 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIN3	NM_024832.5	c.533-2517G>C		intron_variant	Intron 5 of 9	ENST00000216487.12	NP_079108.3
RIN3	NM_001319987.2	c.308-2517G>C		intron_variant	Intron 4 of 8		NP_001306916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIN3	ENST00000216487.12	c.533-2517G>C		intron_variant	Intron 5 of 9	1	NM_024832.5	ENSP00000216487.7
RIN3	ENST00000555589.5	n.460-2517G>C		intron_variant	Intron 4 of 8	1		ENSP00000450682.1
RIN3	ENST00000620541.4	c.533-2517G>C		intron_variant	Intron 5 of 10	5		ENSP00000480603.1
RIN3	ENST00000418924.6	n.432-2517G>C		intron_variant	Intron 4 of 8	2

Frequencies

GnomAD3 genomes AF: 0.842 AC: 127983 AN: 152050 Hom.: 54027 Cov.: 31

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.880

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.850

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.841

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

GnomAD4 genome AF: 0.842 AC: 128097 AN: 152168 Hom.: 54081 Cov.: 31 AF XY: 0.845 AC XY: 62897 AN XY: 74392

African (AFR) AF: 0.855 AC: 35491 AN: 41506

American (AMR) AF: 0.880 AC: 13464 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.801 AC: 2782 AN: 3472

East Asian (EAS) AF: 0.997 AC: 5152 AN: 5166

South Asian (SAS) AF: 0.850 AC: 4100 AN: 4826

European-Finnish (FIN) AF: 0.849 AC: 8995 AN: 10600

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.815 AC: 55414 AN: 67988

Other (OTH) AF: 0.843 AC: 1781 AN: 2112

Alfa AF: 0.796 Hom.: 2475

Bravo AF: 0.846

Asia WGS AF: 0.889 AC: 3089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.085
DANN	Benign	0.46
PhyloP100		-1.3
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: rs754388; hg19: chr14-93115410;