dbSNP rs201808974: RPGRIP1L:c.883-32_883-30delAAT (chr16-53673045-CATT-C) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_015272.5(RPGRIP1L):c.883-32_883-30delAAT 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

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.612

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 was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPGRIP1L	NM_015272.5 link	c.883-32_883-30delAAT		intron_variant	Intron 7 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.883-32_883-30delAAT		intron_variant	Intron 7 of 26		NM_015272.5	ENSP00000493946.1		Q68CZ1-1

Frequencies

GnomAD3 genomes

AF:

0.00716

AC:

1089

AN:

152128

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00783

AC:

1871

AN:

238842

AF XY:

0.00817

show subpopulations

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 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.:

AF XY:

0.00648

AC XY:

4650

AN XY:

718122

show subpopulations

Gnomad4 AFR exome

AF:

0.000604

AC:

AN:

33136

Gnomad4 AMR exome

AF:

0.00383

AC:

169

AN:

44096

Gnomad4 ASJ exome

AF:

0.0153

AC:

397

AN:

25868

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39456

Gnomad4 SAS exome

AF:

0.00367

AC:

313

AN:

85264

Gnomad4 FIN exome

AF:

0.0309

AC:

1589

AN:

51486

Gnomad4 NFE exome

AF:

0.00559

AC:

6137

AN:

1098524

Gnomad4 Remaining exome

AF:

0.00629

AC:

375

AN:

59608

Heterozygous variant carriers

422

845

1267

1690

2112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

204

408

612

816

1020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00714

AC:

1087

AN:

152246

Hom.:

Cov.:

AF XY:

0.00834

AC XY:

621

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.000794

AC:

0.000794071

AN:

0.000794071

Gnomad4 AMR

AF:

0.00582

AC:

0.0058208

AN:

0.0058208

Gnomad4 ASJ

AF:

0.0130

AC:

0.0129758

AN:

0.0129758

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00269

AC:

0.00269151

AN:

0.00269151

Gnomad4 FIN

AF:

0.0337

AC:

0.0336665

AN:

0.0336665

Gnomad4 NFE

AF:

0.00768

AC:

0.00767692

AN:

0.00767692

Gnomad4 OTH

AF:

0.0109

AC:

0.0109005

AN:

0.0109005

Heterozygous variant carriers

114

172

229

286

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00891

Hom.:

Bravo

AF:

0.00474

Asia WGS

AF:

0.00145

AC:

AN:

3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

May 28, 2019

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=100/0

polymorphism

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