chr14-92649065-G-C

Position:

• chr14-92649065-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.93).
• 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/exons	MANE	Protein	UniProt
RIN3	NM_024832.5	c.533-2517G>C		intron_variant		ENST00000216487.12	NP_079108.3
RIN3	NM_001319987.2	c.308-2517G>C		intron_variant			NP_001306916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIN3	ENST00000216487.12	c.533-2517G>C		intron_variant		1	NM_024832.5	ENSP00000216487.7
RIN3	ENST00000555589.5	n.460-2517G>C		intron_variant		1		ENSP00000450682.1
RIN3	ENST00000620541.4	c.533-2517G>C		intron_variant		5		ENSP00000480603.1
RIN3	ENST00000418924.6	n.432-2517G>C		intron_variant		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

Gnomad4 AFR AF: 0.855

Gnomad4 AMR AF: 0.880

Gnomad4 ASJ AF: 0.801

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.850

Gnomad4 FIN AF: 0.849

Gnomad4 NFE AF: 0.815

Gnomad4 OTH AF: 0.843

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

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: rs754388; hg19: chr14-93115410;