rs10134299

Positions:

• chr14-92570788-T-G

Variant summary

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

The NM_024832.5(RIN3):​c.250-6572T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 151,950 control chromosomes in the GnomAD database, including 3,649 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 0.20 (3649 hom., cov: 33)
• Consequence: RIN3 NM_024832.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.453

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIN3	NM_024832.5	c.250-6572T>G		intron_variant		ENST00000216487.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIN3	ENST00000216487.12	c.250-6572T>G		intron_variant		1	NM_024832.5	P2
RIN3	ENST00000555589.5	c.250-6572T>G		intron_variant, NMD_transcript_variant		1
RIN3	ENST00000620541.4	c.250-6572T>G		intron_variant		5		A2
RIN3	ENST00000556385.5	n.117-6572T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30300 AN: 151840 Hom.: 3648 Cov.: 33

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.0839

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.200 AC: 30337 AN: 151950 Hom.: 3649 Cov.: 33 AF XY: 0.201 AC XY: 14891 AN XY: 74244

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.0839

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.183

Alfa AF: 0.142 Hom.: 2940

Bravo AF: 0.204

Asia WGS AF: 0.304 AC: 1058 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10134299; hg19: chr14-93037133;