Variant 7-103989356-TGCCGCCGCCGCCGCC-TGCCGCCGCCGCCGCCGCCGCC details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005045.4(RELN):c.-6_-1dupGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,394,188 control chromosomes in the GnomAD database, including 122,293 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.52 ( 20330 hom., cov: 0)

Exomes 𝑓: 0.43 ( 101963 hom. )

Consequence

RELN
NM_005045.4 5_prime_UTR

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 7-103989356-T-TGCCGCC is Benign according to our data. Variant chr7-103989356-T-TGCCGCC is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 130109.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=5}.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RELN	NM_005045.4 link	c.-6_-1dupGGCGGC		5_prime_UTR_variant	1/65	ENST00000428762.6	NP_005036.2	P78509-1
RELN	NM_173054.3 link	c.-6_-1dupGGCGGC		5_prime_UTR_variant	1/64		NP_774959.1	P78509-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6 link	c.-6_-1dupGGCGGC		5_prime_UTR_variant	1/65	5	NM_005045.4	ENSP00000392423.1		P78509-1

Frequencies

GnomAD3 genomes

AF:

0.522

AC:

77298

AN:

148096

Hom.:

20328

Cov.:

show subpopulations

Gnomad AFR

AF:

0.516

Gnomad AMI

AF:

0.423

Gnomad AMR

AF:

0.541

Gnomad ASJ

AF:

0.490

Gnomad EAS

AF:

0.744

Gnomad SAS

AF:

0.675

Gnomad FIN

AF:

0.502

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.501

Gnomad OTH

AF:

0.500

GnomAD3 exomes

AF:

0.147

AC:

9416

AN:

63892

Hom.:

1877

AF XY:

0.156

AC XY:

5772

AN XY:

37010

show subpopulations

Gnomad AFR exome

AF:

0.0576

Gnomad AMR exome

AF:

0.0994

Gnomad ASJ exome

AF:

0.0979

Gnomad EAS exome

AF:

0.284

Gnomad SAS exome

AF:

0.220

Gnomad FIN exome

AF:

0.211

Gnomad NFE exome

AF:

0.136

Gnomad OTH exome

AF:

0.148

GnomAD4 exome

AF:

0.428

AC:

533190

AN:

1245994

Hom.:

101963

Cov.:

AF XY:

0.429

AC XY:

262976

AN XY:

613244

show subpopulations

Gnomad4 AFR exome

AF:

0.431

Gnomad4 AMR exome

AF:

0.278

Gnomad4 ASJ exome

AF:

0.362

Gnomad4 EAS exome

AF:

0.634

Gnomad4 SAS exome

AF:

0.513

Gnomad4 FIN exome

AF:

0.393

Gnomad4 NFE exome

AF:

0.423

Gnomad4 OTH exome

AF:

0.441

GnomAD4 genome

AF:

0.522

AC:

77336

AN:

148194

Hom.:

20330

Cov.:

AF XY:

0.523

AC XY:

37807

AN XY:

72258

show subpopulations

Gnomad4 AFR

AF:

0.516

Gnomad4 AMR

AF:

0.542

Gnomad4 ASJ

AF:

0.490

Gnomad4 EAS

AF:

0.743

Gnomad4 SAS

AF:

0.674

Gnomad4 FIN

AF:

0.502

Gnomad4 NFE

AF:

0.501

Gnomad4 OTH

AF:

0.501

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	May 01, 2013	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 03, 2021

- -

Lissencephaly, Recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Norman-Roberts syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

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.

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