Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015272.5(RPGRIP1L):c.3936C>T(p.Asp1312Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0488 in 1,607,948 control chromosomes in the GnomAD database, including 4,690 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1824 hom., cov: 32)

Exomes 𝑓: 0.043 ( 2866 hom. )

Consequence

RPGRIP1L
NM_015272.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 2.86

Publications

9 publications found

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 Gene-Disease associations (from GenCC):

Meckel syndrome, type 5
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
Joubert syndrome 7
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
COACH syndrome 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Joubert syndrome with renal defect
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Meckel syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

RPGRIP1L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 16-53602088-G-A is Benign according to our data. Variant chr16-53602088-G-A is described in ClinVar as Benign. ClinVar VariationId is 126280.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.86 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015272.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RPGRIP1L	NM_015272.5	MANE Select	c.3936C>T	p.Asp1312Asp	synonymous	Exon 27 of 27	NP_056087.2
RPGRIP1L	NM_001330538.2		c.3834C>T	p.Asp1278Asp	synonymous	Exon 26 of 26	NP_001317467.1
RPGRIP1L	NM_001308334.3		c.3798C>T	p.Asp1266Asp	synonymous	Exon 26 of 26	NP_001295263.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RPGRIP1L	ENST00000647211.2	MANE Select	c.3936C>T	p.Asp1312Asp	synonymous	Exon 27 of 27	ENSP00000493946.1
RPGRIP1L	ENST00000563746.5	TSL:1	c.3834C>T	p.Asp1278Asp	synonymous	Exon 26 of 26	ENSP00000457889.1
RPGRIP1L	ENST00000621565.5	TSL:1	c.3798C>T	p.Asp1266Asp	synonymous	Exon 26 of 26	ENSP00000480698.1

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

15895

AN:

152048

Hom.:

1819

Cov.:

show subpopulations

Gnomad AFR

AF:

0.285

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0557

Gnomad ASJ

AF:

0.0965

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0780

Gnomad FIN

AF:

0.00698

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0332

Gnomad OTH

AF:

0.0889

GnomAD2 exomes

AF:

0.0543

AC:

13580

AN:

250302

AF XY:

0.0517

show subpopulations

Gnomad AFR exome

AF:

0.293

Gnomad AMR exome

AF:

0.0349

Gnomad ASJ exome

AF:

0.104

Gnomad EAS exome

AF:

0.000326

Gnomad FIN exome

AF:

0.00847

Gnomad NFE exome

AF:

0.0331

Gnomad OTH exome

AF:

0.0480

GnomAD4 exome

AF:

0.0429

AC:

62483

AN:

1455782

Hom.:

2866

Cov.:

AF XY:

0.0433

AC XY:

31403

AN XY:

724638

show subpopulations

African (AFR)

AF:

0.297

AC:

9863

AN:

33226

American (AMR)

AF:

0.0371

AC:

1657

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

2727

AN:

26076

East Asian (EAS)

AF:

0.000252

AC:

AN:

39662

South Asian (SAS)

AF:

0.0788

AC:

6779

AN:

86042

European-Finnish (FIN)

AF:

0.00847

AC:

452

AN:

53372

Middle Eastern (MID)

AF:

0.113

AC:

644

AN:

5714

European-Non Finnish (NFE)

AF:

0.0335

AC:

37058

AN:

1106840

Other (OTH)

AF:

0.0547

AC:

3293

AN:

60156

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

2613

5226

7838

10451

13064

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1576

3152

4728

6304

7880

<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:

0.105

AC:

15918

AN:

152166

Hom.:

1824

Cov.:

AF XY:

0.100

AC XY:

7472

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.284

AC:

11786

AN:

41448

American (AMR)

AF:

0.0555

AC:

849

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0965

AC:

335

AN:

3470

East Asian (EAS)

AF:

0.000579

AC:

AN:

5182

South Asian (SAS)

AF:

0.0785

AC:

379

AN:

4828

European-Finnish (FIN)

AF:

0.00698

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0332

AC:

2255

AN:

68022

Other (OTH)

AF:

0.0880

AC:

186

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

613

1227

1840

2454

3067

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

328

492

656

820

<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:

0.0532

Hom.:

1371

Bravo

AF:

0.116

Asia WGS

AF:

0.0460

AC:

159

AN:

3478

EpiCase

AF:

0.0396

EpiControl

AF:

0.0428

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Joubert syndrome 7 (2)

Meckel syndrome, type 5 (2)

Joubert syndrome (1)

Meckel-Gruber syndrome;C0431399:Joubert syndrome (1)

Nephronophthisis 8 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.3

(source)

DANN

Benign

0.50

PhyloP100

2.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs4784320

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over