chr14-92636964-C-T

Variant names:

• chr14-92636964-C-T
• rs10498635
• NM_024832.5:c.441-4274C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 48 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024832.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIN3	NM_024832.5	MANE Select	c.441-4274C>T		intron	N/A	NP_079108.3
	RIN3	NM_001319987.2		c.216-4274C>T		intron	N/A	NP_001306916.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIN3	ENST00000216487.12	TSL:1 MANE Select	c.441-4274C>T		intron	N/A	ENSP00000216487.7
	RIN3	ENST00000555589.5	TSL:1	n.368-4274C>T		intron	N/A	ENSP00000450682.1
	RIN3	ENST00000863459.1		c.441-4274C>T		intron	N/A	ENSP00000533518.1

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

African (AFR) AF: 0.0861 AC: 3570 AN: 41456

American (AMR) AF: 0.109 AC: 1666 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 642 AN: 3468

East Asian (EAS) AF: 0.00310 AC: 16 AN: 5168

South Asian (SAS) AF: 0.142 AC: 683 AN: 4800

European-Finnish (FIN) AF: 0.142 AC: 1494 AN: 10540

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12218 AN: 67948

Other (OTH) AF: 0.142 AC: 299 AN: 2110

Alfa AF: 0.168 Hom.: 8141

Bravo AF: 0.132

Asia WGS AF: 0.107 AC: 374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.72
DANN	Benign	0.75
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10498635; hg19: chr14-93103309;