chr14-92563049-G-C

Position:

• chr14-92563049-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.249+7094G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 152,036 control chromosomes in the GnomAD database, including 44,021 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 0.76 (44021 hom., cov: 31)
• Consequence: RIN3 NM_024832.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.354

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIN3	NM_024832.5	c.249+7094G>C		intron_variant		ENST00000216487.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIN3	ENST00000216487.12	c.249+7094G>C		intron_variant		1	NM_024832.5	P2
RIN3	ENST00000555589.5	c.249+7094G>C		intron_variant, NMD_transcript_variant		1
RIN3	ENST00000620541.4	c.249+7094G>C		intron_variant		5		A2
RIN3	ENST00000556385.5	n.116+7094G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115264 AN: 151918 Hom.: 43985 Cov.: 31

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.963

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.743

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

GnomAD4 genome AF: 0.759 AC: 115359 AN: 152036 Hom.: 44021 Cov.: 31 AF XY: 0.761 AC XY: 56579 AN XY: 74322

Gnomad4 AFR AF: 0.784

Gnomad4 AMR AF: 0.780

Gnomad4 ASJ AF: 0.740

Gnomad4 EAS AF: 0.962

Gnomad4 SAS AF: 0.830

Gnomad4 FIN AF: 0.735

Gnomad4 NFE AF: 0.725

Gnomad4 OTH AF: 0.742

Alfa AF: 0.751 Hom.: 5308

Bravo AF: 0.759

Asia WGS AF: 0.872 AC: 3031 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.5
DANN	Benign	0.69

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: rs6575266; hg19: chr14-93029394;