Variant chr14-21288073-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_020366.4(RPGRIP1):c.85+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000913 in 1,556,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000087 ( 0 hom. )

Consequence

RPGRIP1
NM_020366.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00600

Variant links:

Genes affected

RPGRIP1 (HGNC:13436): (RPGR interacting protein 1) This gene encodes a photoreceptor protein that interacts with retinitis pigmentosa GTPase regulator protein and is a key component of cone and rod photoreceptor cells. Mutations in this gene lead to autosomal recessive congenital blindness. [provided by RefSeq, Oct 2008]

RPGRIP1 links:

Genome browser will be placed here

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;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 14-21288073-G-A is Benign according to our data. Variant chr14-21288073-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1152241.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPGRIP1	NM_020366.4 linkuse as main transcript	c.85+12G>A		intron_variant		ENST00000400017.7	NP_065099.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
RPGRIP1	ENST00000400017.7 linkuse as main transcript	c.85+12G>A	intron_variant	1	NM_020366.4	ENSP00000382895	P2	Q96KN7-1
RPGRIP1	ENST00000556336.5 linkuse as main transcript	c.85+12G>A	intron_variant	5		ENSP00000450445
RPGRIP1	ENST00000557771.5 linkuse as main transcript	c.85+12G>A	intron_variant	5		ENSP00000451219	A2

Frequencies

GnomAD3 genomes

AF:

0.000132

AC:

AN:

152004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000946

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000141

AC:

AN:

249010

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

135106

show subpopulations

Gnomad AFR exome

AF:

0.000323

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000325

Gnomad NFE exome

AF:

0.000195

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000869

AC:

122

AN:

1403968

Hom.:

Cov.:

AF XY:

0.0000755

AC XY:

AN XY:

702000

show subpopulations

Gnomad4 AFR exome

AF:

0.000402

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.000318

Gnomad4 NFE exome

AF:

0.0000755

Gnomad4 OTH exome

AF:

0.000154

GnomAD4 genome

AF:

0.000131

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000946

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000216

Hom.:

Bravo

AF:

0.000189

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Leber congenital amaurosis 6;C2750720:Cone-rod dystrophy 13

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 09, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.8

DANN

Benign

0.21

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