rs56345626

Positions:

chr7-103515417-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005045.4(RELN):c.7887T>C(p.Pro2629=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 1,613,810 control chromosomes in the GnomAD database, including 27,618 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2305 hom., cov: 32)

Exomes 𝑓: 0.18 ( 25313 hom. )

Consequence

RELN
NM_005045.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.924

Variant links:

Genes affected

RELN (HGNC:9957): (reelin) This gene encodes a large secreted extracellular matrix protein thought to control cell-cell interactions critical for cell positioning and neuronal migration during brain development. This protein may be involved in schizophrenia, autism, bipolar disorder, major depression and in migration defects associated with temporal lobe epilepsy. Mutations of this gene are associated with autosomal recessive lissencephaly with cerebellar hypoplasia. Two transcript variants encoding distinct isoforms have been identified for this gene. Other transcript variants have been described but their full length nature has not been determined. [provided by RefSeq, Jul 2008]

RELN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 7-103515417-A-G is Benign according to our data. Variant chr7-103515417-A-G is described in ClinVar as [Benign]. Clinvar id is 130142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-103515417-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.924 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RELN	NM_005045.4 linkuse as main transcript	c.7887T>C	p.Pro2629=	synonymous_variant	50/65	ENST00000428762.6	NP_005036.2
RELN	NM_173054.3 linkuse as main transcript	c.7887T>C	p.Pro2629=	synonymous_variant	50/64		NP_774959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6 linkuse as main transcript	c.7887T>C	p.Pro2629=	synonymous_variant	50/65	5	NM_005045.4	ENSP00000392423	P5	P78509-1

Frequencies

GnomAD3 genomes

AF:

0.173

AC:

26230

AN:

152010

Hom.:

2310

Cov.:

show subpopulations

Gnomad AFR

AF:

0.132

Gnomad AMI

AF:

0.181

Gnomad AMR

AF:

0.158

Gnomad ASJ

AF:

0.170

Gnomad EAS

AF:

0.268

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.214

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.188

Gnomad OTH

AF:

0.171

GnomAD3 exomes

AF:

0.180

AC:

45156

AN:

250546

Hom.:

4351

AF XY:

0.181

AC XY:

24526

AN XY:

135418

show subpopulations

Gnomad AFR exome

AF:

0.130

Gnomad AMR exome

AF:

0.146

Gnomad ASJ exome

AF:

0.170

Gnomad EAS exome

AF:

0.269

Gnomad SAS exome

AF:

0.157

Gnomad FIN exome

AF:

0.212

Gnomad NFE exome

AF:

0.184

Gnomad OTH exome

AF:

0.191

GnomAD4 exome

AF:

0.183

AC:

268037

AN:

1461682

Hom.:

25313

Cov.:

AF XY:

0.183

AC XY:

133367

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.130

Gnomad4 AMR exome

AF:

0.148

Gnomad4 ASJ exome

AF:

0.170

Gnomad4 EAS exome

AF:

0.290

Gnomad4 SAS exome

AF:

0.159

Gnomad4 FIN exome

AF:

0.210

Gnomad4 NFE exome

AF:

0.183

Gnomad4 OTH exome

AF:

0.184

GnomAD4 genome

AF:

0.172

AC:

26235

AN:

152128

Hom.:

2305

Cov.:

AF XY:

0.174

AC XY:

12909

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.132

Gnomad4 AMR

AF:

0.158

Gnomad4 ASJ

AF:

0.170

Gnomad4 EAS

AF:

0.268

Gnomad4 SAS

AF:

0.164

Gnomad4 FIN

AF:

0.214

Gnomad4 NFE

AF:

0.188

Gnomad4 OTH

AF:

0.169

Alfa

AF:

0.175

Hom.:

1099

Bravo

AF:

0.167

Asia WGS

AF:

0.199

AC:

693

AN:

3478

EpiCase

AF:

0.188

EpiControl

AF:

0.183

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 07, 2018	- -

Norman-Roberts syndrome

Benign:2

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. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Norman-Roberts syndrome;C4225327:Familial temporal lobe epilepsy 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

7.7

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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