Variant chr16-53703648-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015272.5(RPGRIP1L):c.-8+155C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0421 in 212,652 control chromosomes in the GnomAD database, including 314 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 268 hom., cov: 32)

Exomes 𝑓: 0.030 ( 46 hom. )

Consequence

RPGRIP1L
NM_015272.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.565

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:

FTO (HGNC:24678): (FTO alpha-ketoglutarate dependent dioxygenase) This gene is a nuclear protein of the AlkB related non-haem iron and 2-oxoglutarate-dependent oxygenase superfamily but the exact physiological function of this gene is not known. Other non-heme iron enzymes function to reverse alkylated DNA and RNA damage by oxidative demethylation. Studies in mice and humans indicate a role in nervous and cardiovascular systems and a strong association with body mass index, obesity risk, and type 2 diabetes. [provided by RefSeq, Jul 2011]

FTO links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 16-53703648-G-A is Benign according to our data. Variant chr16-53703648-G-A is described in ClinVar as [Benign]. Clinvar id is 1174271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPGRIP1L	NM_015272.5 linkuse as main transcript	c.-8+155C>T		intron_variant		ENST00000647211.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPGRIP1L	ENST00000647211.2 linkuse as main transcript	c.-8+155C>T		intron_variant			NM_015272.5		Q68CZ1-1

Frequencies

GnomAD3 genomes

AF:

0.0470

AC:

7143

AN:

152114

Hom.:

266

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0984

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0272

Gnomad ASJ

AF:

0.0793

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0652

Gnomad FIN

AF:

0.00697

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0270

Gnomad OTH

AF:

0.0537

GnomAD4 exome

AF:

0.0298

AC:

1801

AN:

60420

Hom.:

Cov.:

AF XY:

0.0307

AC XY:

970

AN XY:

31596

show subpopulations

Gnomad4 AFR exome

AF:

0.0906

Gnomad4 AMR exome

AF:

0.0264

Gnomad4 ASJ exome

AF:

0.0616

Gnomad4 EAS exome

AF:

0.000243

Gnomad4 SAS exome

AF:

0.0583

Gnomad4 FIN exome

AF:

0.0119

Gnomad4 NFE exome

AF:

0.0220

Gnomad4 OTH exome

AF:

0.0297

GnomAD4 genome

AF:

0.0470

AC:

7151

AN:

152232

Hom.:

268

Cov.:

AF XY:

0.0450

AC XY:

3349

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0983

Gnomad4 AMR

AF:

0.0271

Gnomad4 ASJ

AF:

0.0793

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0661

Gnomad4 FIN

AF:

0.00697

Gnomad4 NFE

AF:

0.0270

Gnomad4 OTH

AF:

0.0532

Alfa

AF:

0.0153

Hom.:

Bravo

AF:

0.0493

Asia WGS

AF:

0.0360

AC:

125

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 24, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

1.1

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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