7-103566787-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005045.4(RELN):c.4589-28A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 1,604,664 control chromosomes in the GnomAD database, including 129,804 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 17169 hom., cov: 32)

Exomes 𝑓: 0.39 ( 112635 hom. )

Consequence

RELN
NM_005045.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.256

Publications

19 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 7-103566787-T-C is Benign according to our data. Variant chr7-103566787-T-C is described in ClinVar as Benign. ClinVar VariationId is 259608.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RELN	NM_005045.4 link	c.4589-28A>G		intron_variant	Intron 31 of 64	ENST00000428762.6	NP_005036.2	P78509-1
RELN	NM_173054.3 link	c.4589-28A>G		intron_variant	Intron 31 of 63		NP_774959.1	P78509-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6 link	c.4589-28A>G		intron_variant	Intron 31 of 64	5	NM_005045.4	ENSP00000392423.1		P78509-1

Frequencies

GnomAD3 genomes

AF:

0.461

AC:

70106

AN:

151924

Hom.:

17153

Cov.:

show subpopulations

Gnomad AFR

AF:

0.639

Gnomad AMI

AF:

0.277

Gnomad AMR

AF:

0.457

Gnomad ASJ

AF:

0.359

Gnomad EAS

AF:

0.474

Gnomad SAS

AF:

0.338

Gnomad FIN

AF:

0.364

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.384

Gnomad OTH

AF:

0.479

GnomAD2 exomes

AF:

0.412

AC:

103316

AN:

250738

AF XY:

0.401

show subpopulations

Gnomad AFR exome

AF:

0.645

Gnomad AMR exome

AF:

0.459

Gnomad ASJ exome

AF:

0.354

Gnomad EAS exome

AF:

0.481

Gnomad FIN exome

AF:

0.362

Gnomad NFE exome

AF:

0.389

Gnomad OTH exome

AF:

0.417

GnomAD4 exome

AF:

0.389

AC:

565393

AN:

1452622

Hom.:

112635

Cov.:

AF XY:

0.387

AC XY:

279705

AN XY:

723346

show subpopulations

African (AFR)

AF:

0.652

AC:

21668

AN:

33248

American (AMR)

AF:

0.461

AC:

20600

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.350

AC:

9123

AN:

26054

East Asian (EAS)

AF:

0.472

AC:

18716

AN:

39624

South Asian (SAS)

AF:

0.330

AC:

28389

AN:

86046

European-Finnish (FIN)

AF:

0.360

AC:

19220

AN:

53378

Middle Eastern (MID)

AF:

0.459

AC:

2632

AN:

5740

European-Non Finnish (NFE)

AF:

0.381

AC:

420898

AN:

1103826

Other (OTH)

AF:

0.402

AC:

24147

AN:

60008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

15206

30413

45619

60826

76032

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13278

26556

39834

53112

66390

<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:

0.462

AC:

70169

AN:

152042

Hom.:

17169

Cov.:

AF XY:

0.460

AC XY:

34157

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.639

AC:

26511

AN:

41478

American (AMR)

AF:

0.457

AC:

6986

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.359

AC:

1243

AN:

3466

East Asian (EAS)

AF:

0.473

AC:

2441

AN:

5162

South Asian (SAS)

AF:

0.338

AC:

1628

AN:

4812

European-Finnish (FIN)

AF:

0.364

AC:

3842

AN:

10554

Middle Eastern (MID)

AF:

0.473

AC:

139

AN:

294

European-Non Finnish (NFE)

AF:

0.384

AC:

26115

AN:

67976

Other (OTH)

AF:

0.479

AC:

1011

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1880

3760

5641

7521

9401

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

622

1244

1866

2488

3110

<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:

0.406

Hom.:

51915

Bravo

AF:

0.482

Asia WGS

AF:

0.422

AC:

1468

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 26, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

BayesDel_noAF

Benign

-0.93

CADD

Benign

(source)

DANN

Benign

0.63

PhyloP100

-0.26

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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