Variant 16-53687994-C-T 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_015272.5(RPGRIP1L):c.530-29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0603 in 1,295,766 control chromosomes in the GnomAD database, including 3,812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.053 ( 407 hom., cov: 32)

Exomes 𝑓: 0.061 ( 3405 hom. )

Consequence

RPGRIP1L
NM_015272.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.984

Variant links:

Genes affected

RPGRIP1L (HGNC:29168): (RPGRIP1 like) The protein encoded by this gene can localize to the basal body-centrosome complex or to primary cilia and centrosomes in ciliated cells. The encoded protein has been found to interact with nephrocystin-4. Defects in this gene are a cause of Joubert syndrome type 7 (JBTS7) and Meckel syndrome type 5 (MKS5). [provided by RefSeq, Jun 2016]

RPGRIP1L links:

RPGRIP1L (HGNC:):

RPGRIP1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 0 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 16-53687994-C-T is Benign according to our data. Variant chr16-53687994-C-T is described in ClinVar as [Benign]. Clinvar id is 126281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPGRIP1L	NM_015272.5 linkuse as main transcript	c.530-29G>A		intron_variant		ENST00000647211.2	NP_056087.2	Q68CZ1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPGRIP1L	ENST00000647211.2 linkuse as main transcript	c.530-29G>A		intron_variant			NM_015272.5	ENSP00000493946.1		Q68CZ1-1

Frequencies

GnomAD3 genomes

AF:

0.0535

AC:

8124

AN:

151806

Hom.:

407

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0212

Gnomad AMI

AF:

0.0505

Gnomad AMR

AF:

0.0525

Gnomad ASJ

AF:

0.0572

Gnomad EAS

AF:

0.304

Gnomad SAS

AF:

0.0770

Gnomad FIN

AF:

0.0419

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0543

Gnomad OTH

AF:

0.0565

GnomAD3 exomes

AF:

0.0736

AC:

18274

AN:

248406

Hom.:

1300

AF XY:

0.0717

AC XY:

9643

AN XY:

134442

show subpopulations

Gnomad AFR exome

AF:

0.0203

Gnomad AMR exome

AF:

0.0676

Gnomad ASJ exome

AF:

0.0609

Gnomad EAS exome

AF:

0.315

Gnomad SAS exome

AF:

0.0663

Gnomad FIN exome

AF:

0.0443

Gnomad NFE exome

AF:

0.0528

Gnomad OTH exome

AF:

0.0629

GnomAD4 exome

AF:

0.0612

AC:

69950

AN:

1143842

Hom.:

3405

Cov.:

AF XY:

0.0612

AC XY:

35721

AN XY:

583990

show subpopulations

Gnomad4 AFR exome

AF:

0.0169

Gnomad4 AMR exome

AF:

0.0645

Gnomad4 ASJ exome

AF:

0.0586

Gnomad4 EAS exome

AF:

0.273

Gnomad4 SAS exome

AF:

0.0683

Gnomad4 FIN exome

AF:

0.0457

Gnomad4 NFE exome

AF:

0.0527

Gnomad4 OTH exome

AF:

0.0694

GnomAD4 genome

AF:

0.0535

AC:

8127

AN:

151924

Hom.:

407

Cov.:

AF XY:

0.0543

AC XY:

4031

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.0212

Gnomad4 AMR

AF:

0.0528

Gnomad4 ASJ

AF:

0.0572

Gnomad4 EAS

AF:

0.304

Gnomad4 SAS

AF:

0.0765

Gnomad4 FIN

AF:

0.0419

Gnomad4 NFE

AF:

0.0543

Gnomad4 OTH

AF:

0.0583

Alfa

AF:

0.0503

Hom.:

Bravo

AF:

0.0545

Asia WGS

AF:

0.191

AC:

662

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

Joubert syndrome 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Meckel syndrome, type 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.061

DANN

Benign

0.38

BranchPoint Hunter

0.0

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