chr20-19886612-C-T

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

2

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]

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
RIN2NM_018993.4 linkuse as main transcriptc.-36-2954C>T intron_variant ENST00000255006.12 NP_061866.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RIN2ENST00000255006.12 linkuse as main transcriptc.-36-2954C>T intron_variant 2 NM_018993.4 ENSP00000255006 P1Q8WYP3-1
RIN2ENST00000648440.1 linkuse as main transcriptc.-205C>T 5_prime_UTR_variant 1/12 ENSP00000498085 P1Q8WYP3-1
RIN2ENST00000432334.2 linkuse as main transcriptn.537-2954C>T intron_variant, non_coding_transcript_variant 4
RIN2ENST00000648165.1 linkuse as main transcriptn.618-2954C>T intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.0150
AC:
1731
AN:
115190
Hom.:
61
Cov.:
16
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.:
0
Cov.:
6
AF XY:
0.000374
AC XY:
82
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.:
62
Cov.:
16
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 submitterclinical testingGeneDxAug 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.

Other links and lift over

dbSNP: rs6112633; hg19: chr20-19867256; COSMIC: COSV54788751; COSMIC: COSV54788751; API