dbSNP rs559978421: RPGRIP1L:c.632+16delT (chr16-53687846-CA-C) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_015272.5(RPGRIP1L):c.632+16delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00708 in 1,482,226 control chromosomes in the GnomAD database, including 50 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0050 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0073 ( 47 hom. )

Consequence

RPGRIP1L
NM_015272.5 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.350

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 16-53687846-CA-C is Benign according to our data. Variant chr16-53687846-CA-C is described in ClinVar as [Likely_benign]. Clinvar id is 260610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-53687846-CA-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00503 (763/151818) while in subpopulation NFE AF= 0.00869 (590/67862). AF 95% confidence interval is 0.00811. There are 3 homozygotes in gnomad4. There are 346 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPGRIP1L	NM_015272.5 link	c.632+16delT		intron_variant	Intron 5 of 26	ENST00000647211.2	NP_056087.2	Q68CZ1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPGRIP1L	ENST00000647211.2 link	c.632+16delT		intron_variant	Intron 5 of 26		NM_015272.5	ENSP00000493946.1		Q68CZ1-1

Frequencies

GnomAD3 genomes

AF:

0.00503

AC:

763

AN:

151702

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00179

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00341

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00181

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00869

Gnomad OTH

AF:

0.00385

GnomAD3 exomes

AF:

0.00445

AC:

1112

AN:

249882

Hom.:

AF XY:

0.00453

AC XY:

612

AN XY:

135010

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.00267

Gnomad ASJ exome

AF:

0.00428

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00200

Gnomad NFE exome

AF:

0.00789

Gnomad OTH exome

AF:

0.00328

GnomAD4 exome

AF:

0.00731

AC:

9729

AN:

1330408

Hom.:

Cov.:

AF XY:

0.00702

AC XY:

4703

AN XY:

669700

show subpopulations

Gnomad4 AFR exome

AF:

0.00101

Gnomad4 AMR exome

AF:

0.00245

Gnomad4 ASJ exome

AF:

0.00428

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00164

Gnomad4 NFE exome

AF:

0.00918

Gnomad4 OTH exome

AF:

0.00491

GnomAD4 genome

AF:

0.00503

AC:

763

AN:

151818

Hom.:

Cov.:

AF XY:

0.00466

AC XY:

346

AN XY:

74188

show subpopulations

Gnomad4 AFR

AF:

0.00179

Gnomad4 AMR

AF:

0.00341

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00181

Gnomad4 NFE

AF:

0.00869

Gnomad4 OTH

AF:

0.00381

Alfa

AF:

0.00556

Hom.:

Bravo

AF:

0.00516

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Apr 30, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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