rs2104237

Positions:

• chr14-92572336-T-C

Variant summary

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

The NM_024832.5(RIN3):​c.250-5024T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,076 control chromosomes in the GnomAD database, including 4,259 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 0.21 (4259 hom., cov: 32)
• Consequence: RIN3 NM_024832.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIN3	NM_024832.5	c.250-5024T>C		intron_variant		ENST00000216487.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIN3	ENST00000216487.12	c.250-5024T>C		intron_variant		1	NM_024832.5	P2
RIN3	ENST00000555589.5	c.250-5024T>C		intron_variant, NMD_transcript_variant		1
RIN3	ENST00000620541.4	c.250-5024T>C		intron_variant		5		A2
RIN3	ENST00000556385.5	n.117-5024T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32158 AN: 151958 Hom.: 4255 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.0838

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.212 AC: 32201 AN: 152076 Hom.: 4259 Cov.: 32 AF XY: 0.212 AC XY: 15761 AN XY: 74356

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.0838

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.196

Alfa AF: 0.177 Hom.: 535

Bravo AF: 0.220

Asia WGS AF: 0.308 AC: 1071 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.4
DANN	Benign	0.61

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: rs2104237; hg19: chr14-93038681;