7-103989356-TGCCGCCGCCGCCGCC-TGCCGCCGCCGCCGCCGCCGCC

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

lissencephaly with cerebellar hypoplasia
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Norman-Roberts syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P, PanelApp Australia
familial temporal lobe epilepsy 7
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
autosomal dominant epilepsy with auditory features
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
ankylosing spondylitis
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
complex neurodevelopmental disorder
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

RELN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 130109.

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 rank	MANE	Protein	UniProt
RELN	NM_005045.4 link	c.-6_-1dupGGCGGC		5_prime_UTR_variant	Exon 1 of 65	ENST00000428762.6	NP_005036.2
RELN	NM_173054.3 link	c.-6_-1dupGGCGGC		5_prime_UTR_variant	Exon 1 of 64		NP_774959.1

Ensembl

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

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

GnomAD2 exomes

AF:

0.147

AC:

9416

AN:

63892

AF XY:

0.156

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 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

African (AFR)

AF:

0.431

AC:

10529

AN:

24454

American (AMR)

AF:

0.278

AC:

5676

AN:

20450

Ashkenazi Jewish (ASJ)

AF:

0.362

AC:

7491

AN:

20696

East Asian (EAS)

AF:

0.634

AC:

17115

AN:

26976

South Asian (SAS)

AF:

0.513

AC:

27905

AN:

54362

European-Finnish (FIN)

AF:

0.393

AC:

14567

AN:

37094

Middle Eastern (MID)

AF:

0.439

AC:

1806

AN:

4118

European-Non Finnish (NFE)

AF:

0.423

AC:

425446

AN:

1006444

Other (OTH)

AF:

0.441

AC:

22655

AN:

51400

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.527

Heterozygous variant carriers

10781

21562

32343

43124

53905

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14068

28136

42204

56272

70340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.522

AC:

77336

AN:

148194

Hom.:

20330

Cov.:

AF XY:

0.523

AC XY:

37807

AN XY:

72258

show subpopulations

African (AFR)

AF:

0.516

AC:

20756

AN:

40260

American (AMR)

AF:

0.542

AC:

8148

AN:

15024

Ashkenazi Jewish (ASJ)

AF:

0.490

AC:

1690

AN:

3446

East Asian (EAS)

AF:

0.743

AC:

3489

AN:

4694

South Asian (SAS)

AF:

0.674

AC:

3160

AN:

4688

European-Finnish (FIN)

AF:

0.502

AC:

5040

AN:

10046

Middle Eastern (MID)

AF:

0.565

AC:

157

AN:

278

European-Non Finnish (NFE)

AF:

0.501

AC:

33489

AN:

66812

Other (OTH)

AF:

0.501

AC:

1031

AN:

2058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1753

3505

5258

7010

8763

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

680

1360

2040

2720

3400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.349

Hom.:

609

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

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 01, 2013

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Benign:1

Nov 03, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Lissencephaly, Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Norman-Roberts syndrome

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over