Variant 8-10606797-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 ENST00000382483.4(RP1L1):c.*98C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 1,582,082 control chromosomes in the GnomAD database, including 140,480 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14056 hom., cov: 34)

Exomes 𝑓: 0.41 ( 126424 hom. )

Consequence

RP1L1
ENST00000382483.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.520

Variant links:

Genes affected

RP1L1 (HGNC:15946): (RP1 like 1) This gene encodes a member of the doublecortin family. The protein encoded by this gene contains two N-terminal doublecortin domains, which bind microtubules and regulate microtubule polymerization, and two C-terminal large repetitive regions, both of which contain a high percentage of glutamine and glutamic acid residues. This protein is a retinal-specific protein. Its exact length varies among individuals due to the presence of a 16aa repeat in the first C-terminal repetitive region. The 16aa repeat is encoded by the highly polymorphic 48-bp repeat, and 1-6 copies of the 16aa repeat have been identified in normal individuals. The current reference sequence shown here has a single copy of the 16aa repeat. This protein and the RP1 protein, another retinal-specific protein, play essential and synergistic roles in affecting photosensitivity and outer segment morphogenesis of rod photoreceptors. Mutations in this gene cause occult macular dystrophy (OMD). [provided by RefSeq, Sep 2010]

RP1L1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

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

BP6

Variant 8-10606797-G-A is Benign according to our data. Variant chr8-10606797-G-A is described in ClinVar as [Benign]. Clinvar id is 361200.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RP1L1	NM_178857.6 linkuse as main transcript	c.*98C>T		3_prime_UTR_variant	4/4	ENST00000382483.4	NP_849188.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RP1L1	ENST00000382483.4 linkuse as main transcript	c.*98C>T		3_prime_UTR_variant	4/4	1	NM_178857.6	ENSP00000371923	P1	Q8IWN7-1

Frequencies

GnomAD3 genomes

AF:

0.421

AC:

63945

AN:

152020

Hom.:

14042

Cov.:

show subpopulations

Gnomad AFR

AF:

0.357

Gnomad AMI

AF:

0.478

Gnomad AMR

AF:

0.512

Gnomad ASJ

AF:

0.374

Gnomad EAS

AF:

0.554

Gnomad SAS

AF:

0.567

Gnomad FIN

AF:

0.587

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.394

Gnomad OTH

AF:

0.430

GnomAD4 exome

AF:

0.415

AC:

592748

AN:

1429944

Hom.:

126424

Cov.:

AF XY:

0.418

AC XY:

297404

AN XY:

710720

show subpopulations

Gnomad4 AFR exome

AF:

0.351

Gnomad4 AMR exome

AF:

0.622

Gnomad4 ASJ exome

AF:

0.367

Gnomad4 EAS exome

AF:

0.544

Gnomad4 SAS exome

AF:

0.559

Gnomad4 FIN exome

AF:

0.554

Gnomad4 NFE exome

AF:

0.389

Gnomad4 OTH exome

AF:

0.412

GnomAD4 genome

AF:

0.421

AC:

64000

AN:

152138

Hom.:

14056

Cov.:

AF XY:

0.437

AC XY:

32474

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.358

Gnomad4 AMR

AF:

0.512

Gnomad4 ASJ

AF:

0.374

Gnomad4 EAS

AF:

0.555

Gnomad4 SAS

AF:

0.567

Gnomad4 FIN

AF:

0.587

Gnomad4 NFE

AF:

0.394

Gnomad4 OTH

AF:

0.425

Alfa

AF:

0.402

Hom.:

25823

Bravo

AF:

0.417

Asia WGS

AF:

0.533

AC:

1852

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Occult macular dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.14

DANN

Benign

0.54

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