Variant 19-47834289-A-G 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_000554.6(CRX):c.-35-120A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 695,998 control chromosomes in the GnomAD database, including 429 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 265 hom., cov: 32)

Exomes 𝑓: 0.012 ( 164 hom. )

Consequence

CRX
NM_000554.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.27

Variant links:

Genes affected

CRX (HGNC:2383): (cone-rod homeobox) The protein encoded by this gene is a photoreceptor-specific transcription factor which plays a role in the differentiation of photoreceptor cells. This homeodomain protein is necessary for the maintenance of normal cone and rod function. Mutations in this gene are associated with photoreceptor degeneration, Leber congenital amaurosis type III and the autosomal dominant cone-rod dystrophy 2. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some variants has not been determined. [provided by RefSeq, Jul 2008]

CRX 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=-0.88).

BP6

Variant 19-47834289-A-G is Benign according to our data. Variant chr19-47834289-A-G is described in ClinVar as [Benign]. Clinvar id is 1231525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRX	NM_000554.6 linkuse as main transcript	c.-35-120A>G		intron_variant		ENST00000221996.12	NP_000545.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
CRX	ENST00000221996.12 linkuse as main transcript	c.-35-120A>G	intron_variant	2	NM_000554.6	ENSP00000221996	P1
CRX	ENST00000556527.1 linkuse as main transcript	n.78-1954A>G	intron_variant, non_coding_transcript_variant	1
CRX	ENST00000566686.5 linkuse as main transcript	c.-35-120A>G	intron_variant	5		ENSP00000457808
CRX	ENST00000613299.1 linkuse as main transcript	c.-35-120A>G	intron_variant	3		ENSP00000478106

Frequencies

GnomAD3 genomes

AF:

0.0359

AC:

5456

AN:

152180

Hom.:

263

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.0789

Gnomad AMR

AF:

0.0226

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.0298

Gnomad SAS

AF:

0.0182

Gnomad FIN

AF:

0.00103

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00156

Gnomad OTH

AF:

0.0316

GnomAD4 exome

AF:

0.0115

AC:

6271

AN:

543700

Hom.:

164

AF XY:

0.0108

AC XY:

3157

AN XY:

292234

show subpopulations

Gnomad4 AFR exome

AF:

0.112

Gnomad4 AMR exome

AF:

0.0220

Gnomad4 ASJ exome

AF:

0.00571

Gnomad4 EAS exome

AF:

0.0507

Gnomad4 SAS exome

AF:

0.0165

Gnomad4 FIN exome

AF:

0.00173

Gnomad4 NFE exome

AF:

0.00146

Gnomad4 OTH exome

AF:

0.0159

GnomAD4 genome

AF:

0.0359

AC:

5471

AN:

152298

Hom.:

265

Cov.:

AF XY:

0.0355

AC XY:

2646

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.111

Gnomad4 AMR

AF:

0.0226

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.0299

Gnomad4 SAS

AF:

0.0184

Gnomad4 FIN

AF:

0.00103

Gnomad4 NFE

AF:

0.00156

Gnomad4 OTH

AF:

0.0313

Alfa

AF:

0.0287

Hom.:

Bravo

AF:

0.0407

Asia WGS

AF:

0.0420

AC:

145

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	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.24

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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