Variant 20-19886612-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_018993.4(RIN2):c.-36-2954C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.015 ( 62 hom., cov: 16)

Exomes 𝑓: 0.00038 ( 0 hom. )

Consequence

RIN2
NM_018993.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.852

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 20-19886612-C-T is Benign according to our data. Variant chr20-19886612-C-T is described in ClinVar as [Benign]. Clinvar id is 1228223.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIN2	NM_018993.4 linkuse as main transcript	c.-36-2954C>T		intron_variant		ENST00000255006.12	NP_061866.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIN2	ENST00000255006.12 linkuse as main transcript	c.-36-2954C>T	intron_variant		2	NM_018993.4	ENSP00000255006	P1	Q8WYP3-1
RIN2	ENST00000648440.1 linkuse as main transcript	c.-205C>T	5_prime_UTR_variant	1/12			ENSP00000498085	P1	Q8WYP3-1
RIN2	ENST00000432334.2 linkuse as main transcript	n.537-2954C>T	intron_variant, non_coding_transcript_variant		4
RIN2	ENST00000648165.1 linkuse as main transcript	n.618-2954C>T	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0150

AC:

1731

AN:

115190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0557

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00541

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000293

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.0150

GnomAD4 exome

AF:

0.000382

AC:

155

AN:

405554

Hom.:

Cov.:

AF XY:

0.000374

AC XY:

AN XY:

219132

show subpopulations

Gnomad4 AFR exome

AF:

0.0110

Gnomad4 AMR exome

AF:

0.000918

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000821

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.000122

Gnomad4 NFE exome

AF:

0.0000852

Gnomad4 OTH exome

AF:

0.000605

GnomAD4 genome

AF:

0.0150

AC:

1732

AN:

115178

Hom.:

Cov.:

AF XY:

0.0147

AC XY:

796

AN XY:

54180

show subpopulations

Gnomad4 AFR

AF:

0.0557

Gnomad4 AMR

AF:

0.00532

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000295

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.0149

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 08, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.53

DANN

Benign

0.44

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

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