rs201808974

chr16-53673045-CATT-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.883-32_883-30del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00634 in 1,594,690 control chromosomes in the GnomAD database, including 79 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0071 (11 hom., cov: 32)
  • Exomes 𝑓: 0.0063 (68 hom.)
• Consequence: RPGRIP1L NM_015272.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.612

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 16-53673045-CATT-C is Benign according to our data. Variant chr16-53673045-CATT-C is described in ClinVar as [Likely_benign]. Clinvar id is 260612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00714 (1087/152246) while in subpopulation NFE AF= 0.00768 (522/67996). AF 95% confidence interval is 0.00713. There are 11 homozygotes in gnomad4. There are 621 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPGRIP1L	NM_015272.5	c.883-32_883-30del		intron_variant		ENST00000647211.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPGRIP1L	ENST00000647211.2	c.883-32_883-30del		intron_variant			NM_015272.5

Frequencies

GnomAD3 genomes AF: 0.00716 AC: 1089 AN: 152128 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.000796

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00583

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.0337

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00768

Gnomad OTH AF: 0.0115

GnomAD3 exomes AF: 0.00783 AC: 1871 AN: 238842 Hom.: 16 AF XY: 0.00817 AC XY: 1058 AN XY: 129520

Gnomad AFR exome AF: 0.000401

Gnomad AMR exome AF: 0.00369

Gnomad ASJ exome AF: 0.0163

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00351

Gnomad FIN exome AF: 0.0311

Gnomad NFE exome AF: 0.00748

Gnomad OTH exome AF: 0.00873

GnomAD4 exome AF: 0.00625 AC: 9022 AN: 1442444 Hom.: 68 AF XY: 0.00648 AC XY: 4650 AN XY: 718122

Gnomad4 AFR exome AF: 0.000604

Gnomad4 AMR exome AF: 0.00383

Gnomad4 ASJ exome AF: 0.0153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00367

Gnomad4 FIN exome AF: 0.0309

Gnomad4 NFE exome AF: 0.00559

Gnomad4 OTH exome AF: 0.00629

GnomAD4 genome AF: 0.00714 AC: 1087 AN: 152246 Hom.: 11 Cov.: 32 AF XY: 0.00834 AC XY: 621 AN XY: 74440

Gnomad4 AFR AF: 0.000794

Gnomad4 AMR AF: 0.00582

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.0337

Gnomad4 NFE AF: 0.00768

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00891 Hom.: 2

Bravo AF: 0.00474

Asia WGS AF: 0.00145 AC: 5 AN: 3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs201808974; hg19: chr16-53706957;