Variant X-18641857-TA-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000330.4(RS1):c.*146del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.050 ( 293 hom., 1231 hem., cov: 20)

Exomes 𝑓: 0.14 ( 49 hom. 345 hem. )

Consequence

RS1
NM_000330.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.54

Variant links:

Genes affected

RS1 (HGNC:10457): (retinoschisin 1) This gene encodes an extracellular protein that plays a crucial role in the cellular organization of the retina. The encoded protein is assembled and secreted from photoreceptors and bipolar cells as a homo-oligomeric protein complex. Mutations in this gene are responsible for X-linked retinoschisis, a common, early-onset macular degeneration in males that results in a splitting of the inner layers of the retina and severe loss in vision. [provided by RefSeq, Oct 2008]

RS1 links:

CDKL5 (HGNC:11411): (cyclin dependent kinase like 5) This gene is a member of Ser/Thr protein kinase family and encodes a phosphorylated protein with protein kinase activity. Mutations in this gene have been associated with X-linked infantile spasm syndrome (ISSX), also known as X-linked West syndrome, and Rett syndrome (RTT). Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

CDKL5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant X-18641857-TA-T is Benign according to our data. Variant chrX-18641857-TA-T is described in ClinVar as [Benign]. Clinvar id is 1272473.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
RS1	NM_000330.4 linkuse as main transcript	c.*146del	3_prime_UTR_variant	6/6	ENST00000379984.4
RS1	XM_047442337.1 linkuse as main transcript	c.*146del	3_prime_UTR_variant	4/4
CDKL5	NM_001037343.2 linkuse as main transcript	c.2714-4137del	intron_variant
CDKL5	NM_003159.3 linkuse as main transcript	c.2714-4137del	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RS1	ENST00000379984.4 linkuse as main transcript	c.*146del	3_prime_UTR_variant	6/6	1	NM_000330.4	P1
CDKL5	ENST00000379989.6 linkuse as main transcript	c.2714-4137del	intron_variant		1			O76039-1
CDKL5	ENST00000379996.7 linkuse as main transcript	c.2714-4137del	intron_variant		1			O76039-1

Frequencies

GnomAD3 genomes

AF:

0.0496

AC:

5188

AN:

104570

Hom.:

292

Cov.:

AF XY:

0.0418

AC XY:

1232

AN XY:

29500

show subpopulations

Gnomad AFR

AF:

0.157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0157

Gnomad ASJ

AF:

0.0300

Gnomad EAS

AF:

0.000294

Gnomad SAS

AF:

0.00481

Gnomad FIN

AF:

0.00862

Gnomad MID

AF:

0.0482

Gnomad NFE

AF:

0.00598

Gnomad OTH

AF:

0.0473

GnomAD4 exome

AF:

0.145

AC:

36862

AN:

254271

Hom.:

Cov.:

AF XY:

0.00556

AC XY:

345

AN XY:

62017

show subpopulations

Gnomad4 AFR exome

AF:

0.284

Gnomad4 AMR exome

AF:

0.180

Gnomad4 ASJ exome

AF:

0.175

Gnomad4 EAS exome

AF:

0.153

Gnomad4 SAS exome

AF:

0.0977

Gnomad4 FIN exome

AF:

0.148

Gnomad4 NFE exome

AF:

0.138

Gnomad4 OTH exome

AF:

0.163

GnomAD4 genome

AF:

0.0496

AC:

5185

AN:

104574

Hom.:

293

Cov.:

AF XY:

0.0417

AC XY:

1231

AN XY:

29522

show subpopulations

Gnomad4 AFR

AF:

0.156

Gnomad4 AMR

AF:

0.0157

Gnomad4 ASJ

AF:

0.0300

Gnomad4 EAS

AF:

0.000296

Gnomad4 SAS

AF:

0.00526

Gnomad4 FIN

AF:

0.00862

Gnomad4 NFE

AF:

0.00594

Gnomad4 OTH

AF:

0.0468

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 05, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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