rs1062831

Positions:

Variant summary

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

The NM_005045.4(RELN):c.10074A>G(p.Ala3358=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,613,946 control chromosomes in the GnomAD database, including 13,521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 3281 hom., cov: 33)

Exomes 𝑓: 0.10 ( 10240 hom. )

Consequence

RELN
NM_005045.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -2.35

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:

SLC26A5-AS1 (HGNC:55680): (SLC26A5 antisense RNA 1)

SLC26A5-AS1 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=-0.95).

BP6

Variant 7-103483760-T-C is Benign according to our data. Variant chr7-103483760-T-C is described in ClinVar as [Benign]. Clinvar id is 95209.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-103483760-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.35 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RELN	NM_005045.4 linkuse as main transcript	c.10074A>G	p.Ala3358=	synonymous_variant	62/65	ENST00000428762.6
SLC26A5-AS1	NR_110141.1 linkuse as main transcript	n.1366-20644T>C		intron_variant, non_coding_transcript_variant
RELN	NM_173054.3 linkuse as main transcript	c.10074A>G	p.Ala3358=	synonymous_variant	62/64

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RELN	ENST00000428762.6 linkuse as main transcript	c.10074A>G	p.Ala3358=	synonymous_variant	62/65	5	NM_005045.4	P5	P78509-1
SLC26A5-AS1	ENST00000422488.1 linkuse as main transcript	n.1366-20644T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.173

AC:

26341

AN:

152128

Hom.:

3262

Cov.:

show subpopulations

Gnomad AFR

AF:

0.347

Gnomad AMI

AF:

0.114

Gnomad AMR

AF:

0.138

Gnomad ASJ

AF:

0.0847

Gnomad EAS

AF:

0.257

Gnomad SAS

AF:

0.184

Gnomad FIN

AF:

0.0546

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.0924

Gnomad OTH

AF:

0.163

GnomAD3 exomes

AF:

0.132

AC:

33258

AN:

251074

Hom.:

3087

AF XY:

0.130

AC XY:

17597

AN XY:

135680

show subpopulations

Gnomad AFR exome

AF:

0.351

Gnomad AMR exome

AF:

0.111

Gnomad ASJ exome

AF:

0.0857

Gnomad EAS exome

AF:

0.274

Gnomad SAS exome

AF:

0.176

Gnomad FIN exome

AF:

0.0538

Gnomad NFE exome

AF:

0.0935

Gnomad OTH exome

AF:

0.106

GnomAD4 exome

AF:

0.104

AC:

152127

AN:

1461700

Hom.:

10240

Cov.:

AF XY:

0.105

AC XY:

76713

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.350

Gnomad4 AMR exome

AF:

0.116

Gnomad4 ASJ exome

AF:

0.0855

Gnomad4 EAS exome

AF:

0.260

Gnomad4 SAS exome

AF:

0.171

Gnomad4 FIN exome

AF:

0.0559

Gnomad4 NFE exome

AF:

0.0871

Gnomad4 OTH exome

AF:

0.121

GnomAD4 genome

AF:

0.173

AC:

26414

AN:

152246

Hom.:

3281

Cov.:

AF XY:

0.172

AC XY:

12833

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.348

Gnomad4 AMR

AF:

0.138

Gnomad4 ASJ

AF:

0.0847

Gnomad4 EAS

AF:

0.256

Gnomad4 SAS

AF:

0.184

Gnomad4 FIN

AF:

0.0546

Gnomad4 NFE

AF:

0.0924

Gnomad4 OTH

AF:

0.168

Alfa

AF:

0.132

Hom.:

1090

Bravo

AF:

0.185

Asia WGS

AF:

0.269

AC:

937

AN:

3478

EpiCase

AF:

0.0956

EpiControl

AF:

0.0947

ClinVar

Significance: Benign

Submissions summary: Benign:11

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 DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus 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. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 03, 2012	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Norman-Roberts syndrome

Benign:3

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -
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:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.95

CADD

Benign

0.0070

DANN

Benign

0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

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