Variant 20-19886698-CT-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_018993.4(RIN2):c.-36-2865del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00409 in 1,539,418 control chromosomes in the GnomAD database, including 200 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 97 hom., cov: 29)

Exomes 𝑓: 0.0023 ( 103 hom. )

Consequence

RIN2
NM_018993.4 intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 0.244

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 20-19886698-CT-C is Benign according to our data. Variant chr20-19886698-CT-C is described in ClinVar as [Benign]. Clinvar id is 445625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.07 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.-36-2865del		intron_variant		ENST00000255006.12

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIN2	ENST00000255006.12 linkuse as main transcript	c.-36-2865del	intron_variant		2	NM_018993.4	P1	Q8WYP3-1
RIN2	ENST00000648440.1 linkuse as main transcript	c.-116del	5_prime_UTR_variant	1/12			P1	Q8WYP3-1
RIN2	ENST00000432334.2 linkuse as main transcript	n.537-2865del	intron_variant, non_coding_transcript_variant		4
RIN2	ENST00000648165.1 linkuse as main transcript	n.618-2865del	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0209

AC:

3093

AN:

148220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0722

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00936

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000213

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000385

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.00397

AC:

596

AN:

150168

Hom.:

AF XY:

0.00336

AC XY:

271

AN XY:

80614

show subpopulations

Gnomad AFR exome

AF:

0.0684

Gnomad AMR exome

AF:

0.00358

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000222

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000377

Gnomad OTH exome

AF:

0.00206

GnomAD4 exome

AF:

0.00230

AC:

3205

AN:

1391094

Hom.:

103

Cov.:

AF XY:

0.00206

AC XY:

1415

AN XY:

686086

show subpopulations

Gnomad4 AFR exome

AF:

0.0728

Gnomad4 AMR exome

AF:

0.00448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000253

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000414

Gnomad4 OTH exome

AF:

0.00498

GnomAD4 genome

AF:

0.0209

AC:

3098

AN:

148324

Hom.:

Cov.:

AF XY:

0.0198

AC XY:

1427

AN XY:

72064

show subpopulations

Gnomad4 AFR

AF:

0.0721

Gnomad4 AMR

AF:

0.00935

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000213

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000385

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.00281

Hom.:

Asia WGS

AF:

0.00491

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	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	May 30, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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