rs10498635

chr14-92636964-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024832.5(RIN3):c.441-4274C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 151,962 control chromosomes in the GnomAD database, including 1,645 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 0.14 (1645 hom., cov: 31)
• Consequence: RIN3 NM_024832.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.637

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIN3	NM_024832.5	c.441-4274C>T		intron_variant		ENST00000216487.12
RIN3	NM_001319987.2	c.216-4274C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIN3	ENST00000216487.12	c.441-4274C>T		intron_variant		1	NM_024832.5	P2

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20852 AN: 151844 Hom.: 1645 Cov.: 31

Gnomad AFR AF: 0.0859

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.00309

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.137 AC: 20866 AN: 151962 Hom.: 1645 Cov.: 31 AF XY: 0.133 AC XY: 9905 AN XY: 74252

Gnomad4 AFR AF: 0.0861

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.00310

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.142

Alfa AF: 0.174 Hom.: 3771

Bravo AF: 0.132

Asia WGS AF: 0.107 AC: 374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.72
Dann	Benign	0.75

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: rs10498635; hg19: chr14-93103309;