Genetic Variant RELN:c.-15_-1dupGGCGGCGGCGGCGGC (chr7-103989356-T-TGCCGCCGCCGCCGCC) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_005045.4(RELN):c.-15_-1dupGGCGGCGGCGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.035 ( 151 hom., cov: 0)

Exomes 𝑓: 0.023 ( 709 hom. )

Failed GnomAD Quality Control

Consequence

RELN
NM_005045.4 5_prime_UTR

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: 2.06

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 -9 ACMG points.

BP6

Variant 7-103989356-T-TGCCGCCGCCGCCGCC is Benign according to our data. Variant chr7-103989356-T-TGCCGCCGCCGCCGCC is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 358425.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RELN	NM_005045.4 link	c.-15_-1dupGGCGGCGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 65	ENST00000428762.6	NP_005036.2	P78509-1
RELN	NM_173054.3 link	c.-15_-1dupGGCGGCGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 64		NP_774959.1	P78509-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6 link	c.-15_-1dupGGCGGCGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 65	5	NM_005045.4	ENSP00000392423.1		P78509-1

Frequencies

GnomAD3 genomes

AF:

0.0351

AC:

5197

AN:

148234

Hom.:

152

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0238

Gnomad AMI

AF:

0.0280

Gnomad AMR

AF:

0.0449

Gnomad ASJ

AF:

0.0258

Gnomad EAS

AF:

0.0914

Gnomad SAS

AF:

0.123

Gnomad FIN

AF:

0.0272

Gnomad MID

AF:

0.0405

Gnomad NFE

AF:

0.0309

Gnomad OTH

AF:

0.0447

GnomAD3 exomes

AF:

0.00211

AC:

135

AN:

63892

Hom.:

AF XY:

0.00222

AC XY:

AN XY:

37010

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000266

Gnomad ASJ exome

AF:

0.000499

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00247

Gnomad FIN exome

AF:

0.00475

Gnomad NFE exome

AF:

0.00239

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0232

AC:

29132

AN:

1254916

Hom.:

709

Cov.:

AF XY:

0.0227

AC XY:

14062

AN XY:

618120

show subpopulations

Gnomad4 AFR exome

AF:

0.0172

Gnomad4 AMR exome

AF:

0.0179

Gnomad4 ASJ exome

AF:

0.0128

Gnomad4 EAS exome

AF:

0.0537

Gnomad4 SAS exome

AF:

0.0361

Gnomad4 FIN exome

AF:

0.0166

Gnomad4 NFE exome

AF:

0.0223

Gnomad4 OTH exome

AF:

0.0264

GnomAD4 genome

AF:

0.0350

AC:

5195

AN:

148332

Hom.:

151

Cov.:

AF XY:

0.0359

AC XY:

2597

AN XY:

72342

show subpopulations

Gnomad4 AFR

AF:

0.0238

Gnomad4 AMR

AF:

0.0447

Gnomad4 ASJ

AF:

0.0258

Gnomad4 EAS

AF:

0.0922

Gnomad4 SAS

AF:

0.123

Gnomad4 FIN

AF:

0.0272

Gnomad4 NFE

AF:

0.0309

Gnomad4 OTH

AF:

0.0442

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Benign:2

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Lissencephaly, Recessive

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

RELN-related disorder

Benign:1

Sep 16, 2021

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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.

7-103989356-TGCCGCCGCCGCCGCC-TGCCGCCGCCGCCGCCGCCGCCGCCGCCGCC

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