Variant chr20-19886489-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_018993.4(RIN2):c.-36-3077C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0029 in 543,644 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0079 ( 25 hom., cov: 31)

Exomes 𝑓: 0.00097 ( 4 hom. )

Consequence

RIN2
NM_018993.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0700

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=-0.81).

BP6

Variant 20-19886489-C-T is Benign according to our data. Variant chr20-19886489-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1218108.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00787 (1196/151908) while in subpopulation AFR AF= 0.0278 (1146/41268). AF 95% confidence interval is 0.0264. There are 25 homozygotes in gnomad4. There are 586 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIN2	NM_018993.4 linkuse as main transcript	c.-36-3077C>T		intron_variant		ENST00000255006.12

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
RIN2	ENST00000255006.12 linkuse as main transcript	c.-36-3077C>T	intron_variant	2	NM_018993.4	P1	Q8WYP3-1
RIN2	ENST00000432334.2 linkuse as main transcript	n.537-3077C>T	intron_variant, non_coding_transcript_variant	4
RIN2	ENST00000648165.1 linkuse as main transcript	n.618-3077C>T	intron_variant, non_coding_transcript_variant
RIN2	ENST00000648440.1 linkuse as main transcript		upstream_gene_variant			P1	Q8WYP3-1

Frequencies

GnomAD3 genomes

AF:

0.00774

AC:

1175

AN:

151790

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0273

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00230

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00431

GnomAD4 exome

AF:

0.000973

AC:

381

AN:

391736

Hom.:

Cov.:

AF XY:

0.000881

AC XY:

182

AN XY:

206568

show subpopulations

Gnomad4 AFR exome

AF:

0.0283

Gnomad4 AMR exome

AF:

0.00164

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000348

Gnomad4 NFE exome

AF:

0.0000876

Gnomad4 OTH exome

AF:

0.00159

GnomAD4 genome

AF:

0.00787

AC:

1196

AN:

151908

Hom.:

Cov.:

AF XY:

0.00789

AC XY:

586

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.0278

Gnomad4 AMR

AF:

0.00223

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00596

Hom.:

Bravo

AF:

0.00814

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.88

Splicing

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