Variant rs362726 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

RELN (HGNC:):

RELN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
RELN	NM_005045.4 linkuse as main transcript	c.4589-28A>G		intron_variant		ENST00000428762.6	NP_005036.2	P78509-1
RELN	NM_173054.3 linkuse as main transcript	c.4589-28A>G		intron_variant			NP_774959.1	P78509-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6 linkuse as main transcript	c.4589-28A>G		intron_variant		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

GnomAD3 exomes

AF:

0.412

AC:

103316

AN:

250738

Hom.:

22103

AF XY:

0.401

AC XY:

54406

AN XY:

135530

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 SAS exome

AF:

0.334

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

Gnomad4 AFR exome

AF:

0.652

Gnomad4 AMR exome

AF:

0.461

Gnomad4 ASJ exome

AF:

0.350

Gnomad4 EAS exome

AF:

0.472

Gnomad4 SAS exome

AF:

0.330

Gnomad4 FIN exome

AF:

0.360

Gnomad4 NFE exome

AF:

0.381

Gnomad4 OTH exome

AF:

0.402

GnomAD4 genome

AF:

0.462

AC:

70169

AN:

152042

Hom.:

17169

Cov.:

AF XY:

0.460

AC XY:

34157

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.639

Gnomad4 AMR

AF:

0.457

Gnomad4 ASJ

AF:

0.359

Gnomad4 EAS

AF:

0.473

Gnomad4 SAS

AF:

0.338

Gnomad4 FIN

AF:

0.364

Gnomad4 NFE

AF:

0.384

Gnomad4 OTH

AF:

0.479

Alfa

AF:

0.396

Hom.:

26429

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

BayesDel_noAF

Benign

-0.93

CADD

Benign

DANN

Benign

0.63

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

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