7-103652718-C-T

Position:

chr7-103652718-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_005045.4(RELN):c.1596G>A(p.Gln532Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0291 in 1,612,708 control chromosomes in the GnomAD database, including 866 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 157 hom., cov: 32)

Exomes 𝑓: 0.028 ( 709 hom. )

Consequence

RELN
NM_005045.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.20

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:

RELN (HGNC:):

RELN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 7-103652718-C-T is Benign according to our data. Variant chr7-103652718-C-T is described in ClinVar as [Benign]. Clinvar id is 95212.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-103652718-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.2 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0688 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.1596G>A	p.Gln532Gln	synonymous_variant	14/65	ENST00000428762.6	NP_005036.2	P78509-1
RELN	NM_173054.3 linkuse as main transcript	c.1596G>A	p.Gln532Gln	synonymous_variant	14/64		NP_774959.1	P78509-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6 linkuse as main transcript	c.1596G>A	p.Gln532Gln	synonymous_variant	14/65	5	NM_005045.4	ENSP00000392423.1		P78509-1

Frequencies

GnomAD3 genomes

AF:

0.0385

AC:

5854

AN:

151958

Hom.:

158

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0712

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0286

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.00893

Gnomad FIN

AF:

0.0208

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0305

Gnomad OTH

AF:

0.0311

GnomAD3 exomes

AF:

0.0237

AC:

5938

AN:

250726

Hom.:

108

AF XY:

0.0224

AC XY:

3039

AN XY:

135488

show subpopulations

Gnomad AFR exome

AF:

0.0716

Gnomad AMR exome

AF:

0.0139

Gnomad ASJ exome

AF:

0.0187

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00853

Gnomad FIN exome

AF:

0.0211

Gnomad NFE exome

AF:

0.0288

Gnomad OTH exome

AF:

0.0206

GnomAD4 exome

AF:

0.0281

AC:

41046

AN:

1460632

Hom.:

709

Cov.:

AF XY:

0.0274

AC XY:

19902

AN XY:

726642

show subpopulations

Gnomad4 AFR exome

AF:

0.0739

Gnomad4 AMR exome

AF:

0.0152

Gnomad4 ASJ exome

AF:

0.0190

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00850

Gnomad4 FIN exome

AF:

0.0224

Gnomad4 NFE exome

AF:

0.0304

Gnomad4 OTH exome

AF:

0.0264

GnomAD4 genome

AF:

0.0385

AC:

5853

AN:

152076

Hom.:

157

Cov.:

AF XY:

0.0372

AC XY:

2765

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.0710

Gnomad4 AMR

AF:

0.0286

Gnomad4 ASJ

AF:

0.0176

Gnomad4 EAS

AF:

0.000582

Gnomad4 SAS

AF:

0.00894

Gnomad4 FIN

AF:

0.0208

Gnomad4 NFE

AF:

0.0305

Gnomad4 OTH

AF:

0.0308

Alfa

AF:

0.0334

Hom.:

Bravo

AF:

0.0404

Asia WGS

AF:

0.00635

AC:

AN:

3478

EpiCase

AF:

0.0290

EpiControl

AF:

0.0252

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 23, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 28, 2014	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

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

- -

Norman-Roberts syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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

-0.37

CADD

Benign

7.9

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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