rs559978421

Positions:

• chr16-53687846-CA-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_015272.5(RPGRIP1L):​c.632+16del 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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.350

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]

ACMG classification

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/exons	MANE	Protein	UniProt
RPGRIP1L	NM_015272.5	c.632+16del		intron_variant		ENST00000647211.2	NP_056087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPGRIP1L	ENST00000647211.2	c.632+16del		intron_variant			NM_015272.5	ENSP00000493946

Frequencies

GnomAD3 genomes AF: 0.00503 AC: 763 AN: 151702 Hom.: 3 Cov.: 32

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.: 4 AF XY: 0.00453 AC XY: 612 AN XY: 135010

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.: 47 Cov.: 21 AF XY: 0.00702 AC XY: 4703 AN XY: 669700

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.: 3 Cov.: 32 AF XY: 0.00466 AC XY: 346 AN XY: 74188

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.: 0

Bravo AF: 0.00516

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 30, 2015	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. -

Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs559978421; hg19: chr16-53721758;