Variant chr16-53622363-CAA-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP6_ModerateBS1

The NM_015272.5(RPGRIP1L):c.3295-9_3295-8delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0173 in 421,426 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 30)

Exomes 𝑓: 0.023 ( 0 hom. )

Consequence

RPGRIP1L
NM_015272.5 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.196

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 16-53622363-CAA-C is Benign according to our data. Variant chr16-53622363-CAA-C is described in ClinVar as [Benign]. Clinvar id is 1293752.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0226 (7284/322644) while in subpopulation SAS AF= 0.0393 (1040/26446). AF 95% confidence interval is 0.0373. There are 0 homozygotes in gnomad4_exome. There are 3889 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPGRIP1L	NM_015272.5 linkuse as main transcript	c.3295-9_3295-8delTT		splice_region_variant, 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.3295-9_3295-8delTT		splice_region_variant, intron_variant			NM_015272.5	ENSP00000493946.1		Q68CZ1-1

Frequencies

GnomAD3 genomes

AF:

0.000142

AC:

AN:

98742

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000110

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00117

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000108

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0491

AC:

1316

AN:

26824

Hom.:

AF XY:

0.0495

AC XY:

690

AN XY:

13932

show subpopulations

Gnomad AFR exome

AF:

0.0439

Gnomad AMR exome

AF:

0.0430

Gnomad ASJ exome

AF:

0.0547

Gnomad EAS exome

AF:

0.0458

Gnomad SAS exome

AF:

0.0578

Gnomad FIN exome

AF:

0.0482

Gnomad NFE exome

AF:

0.0530

Gnomad OTH exome

AF:

0.0358

GnomAD4 exome

AF:

0.0226

AC:

7284

AN:

322644

Hom.:

AF XY:

0.0230

AC XY:

3889

AN XY:

169064

show subpopulations

Gnomad4 AFR exome

AF:

0.0220

Gnomad4 AMR exome

AF:

0.0297

Gnomad4 ASJ exome

AF:

0.0226

Gnomad4 EAS exome

AF:

0.0145

Gnomad4 SAS exome

AF:

0.0393

Gnomad4 FIN exome

AF:

0.0173

Gnomad4 NFE exome

AF:

0.0214

Gnomad4 OTH exome

AF:

0.0219

GnomAD4 genome

AF:

0.000142

AC:

AN:

98782

Hom.:

Cov.:

AF XY:

0.000171

AC XY:

AN XY:

46820

show subpopulations

Gnomad4 AFR

AF:

0.000110

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00117

Gnomad4 NFE

AF:

0.000108

Gnomad4 OTH

AF:

0.00

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 submitter

clinical testing

GeneDx

Jan 28, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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