Variant 20-19886762-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018993.4(RIN2):c.-36-2804C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00363 in 1,540,340 control chromosomes in the GnomAD database, including 154 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 82 hom., cov: 29)

Exomes 𝑓: 0.0020 ( 72 hom. )

Consequence

RIN2
NM_018993.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.04

Variant links:

Genes affected

RIN2 (HGNC:18750): (Ras and Rab interactor 2) The RAB5 protein is a small GTPase involved in membrane trafficking in the early endocytic pathway. The protein encoded by this gene binds the GTP-bound form of the RAB5 protein preferentially over the GDP-bound form, and functions as a guanine nucleotide exchange factor for RAB5. The encoded protein is found primarily as a tetramer in the cytoplasm and does not bind other members of the RAB family. Mutations in this gene cause macrocephaly alopecia cutis laxa and scoliosis (MACS) syndrome, an elastic tissue disorder, as well as the related connective tissue disorder, RIN2 syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2011]

RIN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017386973).

BP6

Variant 20-19886762-C-A is Benign according to our data. Variant chr20-19886762-C-A is described in ClinVar as [Benign]. Clinvar id is 695680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIN2	NM_018993.4 linkuse as main transcript	c.-36-2804C>A		intron_variant		ENST00000255006.12

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIN2	ENST00000255006.12 linkuse as main transcript	c.-36-2804C>A	intron_variant		2	NM_018993.4	P1	Q8WYP3-1
RIN2	ENST00000648440.1 linkuse as main transcript	c.-55C>A	5_prime_UTR_variant	1/12			P1	Q8WYP3-1
RIN2	ENST00000432334.2 linkuse as main transcript	n.537-2804C>A	intron_variant, non_coding_transcript_variant		4
RIN2	ENST00000648165.1 linkuse as main transcript	n.618-2804C>A	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0186

AC:

2829

AN:

151982

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0640

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00845

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.0139

GnomAD3 exomes

AF:

0.00357

AC:

508

AN:

142154

Hom.:

AF XY:

0.00307

AC XY:

233

AN XY:

75996

show subpopulations

Gnomad AFR exome

AF:

0.0581

Gnomad AMR exome

AF:

0.00327

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000502

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000353

Gnomad OTH exome

AF:

0.00237

GnomAD4 exome

AF:

0.00198

AC:

2751

AN:

1388242

Hom.:

Cov.:

AF XY:

0.00181

AC XY:

1241

AN XY:

684834

show subpopulations

Gnomad4 AFR exome

AF:

0.0621

Gnomad4 AMR exome

AF:

0.00376

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000155

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000403

Gnomad4 OTH exome

AF:

0.00443

GnomAD4 genome

AF:

0.0186

AC:

2835

AN:

152098

Hom.:

Cov.:

AF XY:

0.0173

AC XY:

1289

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0639

Gnomad4 AMR

AF:

0.00844

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00666

Hom.:

Bravo

AF:

0.0217

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00130

AC:

ExAC

AF:

0.00302

AC:

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 07, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.81

Cadd

Benign

4.0

Dann

Benign

0.97

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.37

MetaRNN

Benign

0.0017

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

0.19

REVEL

Benign

0.010

Sift

Benign

0.52

Sift4G

Benign

0.83

Vest4

0.15

MutPred

0.14

Gain of MoRF binding (P = 0.1223);

MVP

0.26

MPC

0.22

ClinPred

0.013

GERP RS

-6.5

gMVP

0.047

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over