rs2075038

Positions:

chr7-103522160-G-A

Variant summary

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

The NM_005045.4(RELN):c.7530C>T(p.Pro2510=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.042 in 1,613,916 control chromosomes in the GnomAD database, including 2,145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 158 hom., cov: 31)

Exomes 𝑓: 0.042 ( 1987 hom. )

Consequence

RELN
NM_005045.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.51

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=-0.74).

BP6

Variant 7-103522160-G-A is Benign according to our data. Variant chr7-103522160-G-A is described in ClinVar as [Benign]. Clinvar id is 130141.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-103522160-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.51 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.14 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.7530C>T	p.Pro2510=	synonymous_variant	48/65	ENST00000428762.6	NP_005036.2
RELN	NM_173054.3 linkuse as main transcript	c.7530C>T	p.Pro2510=	synonymous_variant	48/64		NP_774959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6 linkuse as main transcript	c.7530C>T	p.Pro2510=	synonymous_variant	48/65	5	NM_005045.4	ENSP00000392423	P5	P78509-1

Frequencies

GnomAD3 genomes

AF:

0.0380

AC:

5770

AN:

152008

Hom.:

159

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0287

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0473

Gnomad ASJ

AF:

0.0617

Gnomad EAS

AF:

0.0222

Gnomad SAS

AF:

0.149

Gnomad FIN

AF:

0.0239

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0356

Gnomad OTH

AF:

0.0492

GnomAD3 exomes

AF:

0.0534

AC:

13431

AN:

251446

Hom.:

578

AF XY:

0.0576

AC XY:

7828

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.0267

Gnomad AMR exome

AF:

0.0726

Gnomad ASJ exome

AF:

0.0617

Gnomad EAS exome

AF:

0.0120

Gnomad SAS exome

AF:

0.146

Gnomad FIN exome

AF:

0.0252

Gnomad NFE exome

AF:

0.0377

Gnomad OTH exome

AF:

0.0559

GnomAD4 exome

AF:

0.0424

AC:

61968

AN:

1461790

Hom.:

1987

Cov.:

AF XY:

0.0456

AC XY:

33130

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.0300

Gnomad4 AMR exome

AF:

0.0711

Gnomad4 ASJ exome

AF:

0.0624

Gnomad4 EAS exome

AF:

0.0373

Gnomad4 SAS exome

AF:

0.144

Gnomad4 FIN exome

AF:

0.0249

Gnomad4 NFE exome

AF:

0.0338

Gnomad4 OTH exome

AF:

0.0488

GnomAD4 genome

AF:

0.0381

AC:

5791

AN:

152126

Hom.:

158

Cov.:

AF XY:

0.0392

AC XY:

2917

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0289

Gnomad4 AMR

AF:

0.0476

Gnomad4 ASJ

AF:

0.0617

Gnomad4 EAS

AF:

0.0224

Gnomad4 SAS

AF:

0.149

Gnomad4 FIN

AF:

0.0239

Gnomad4 NFE

AF:

0.0356

Gnomad4 OTH

AF:

0.0511

Alfa

AF:

0.0383

Hom.:

Bravo

AF:

0.0369

Asia WGS

AF:

0.0980

AC:

339

AN:

3478

EpiCase

AF:

0.0357

EpiControl

AF:

0.0373

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Apr 25, 2013	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 31, 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. -
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	-	- -

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 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

-0.74

CADD

Benign

0.12

DANN

Benign

0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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