Variant rs13232021 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.8667+45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,599,828 control chromosomes in the GnomAD database, including 23,417 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1895 hom., cov: 33)

Exomes 𝑓: 0.17 ( 21522 hom. )

Consequence

RELN
NM_005045.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.140

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:

SLC26A5-AS1 (HGNC:55680): (SLC26A5 antisense RNA 1)

SLC26A5-AS1 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=-0.9).

BP6

Variant 7-103500700-A-G is Benign according to our data. Variant chr7-103500700-A-G is described in ClinVar as [Benign]. Clinvar id is 259615.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
RELN	NM_005045.4 linkuse as main transcript	c.8667+45T>C	intron_variant	ENST00000428762.6	NP_005036.2
SLC26A5-AS1	NR_110141.1 linkuse as main transcript	n.1366-3704A>G	intron_variant, non_coding_transcript_variant
RELN	NM_173054.3 linkuse as main transcript	c.8667+45T>C	intron_variant		NP_774959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6 linkuse as main transcript	c.8667+45T>C		intron_variant		5	NM_005045.4	ENSP00000392423	P5	P78509-1
SLC26A5-AS1	ENST00000422488.1 linkuse as main transcript	n.1366-3704A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.148

AC:

22544

AN:

152082

Hom.:

1898

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0854

Gnomad AMI

AF:

0.157

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.135

Gnomad EAS

AF:

0.292

Gnomad SAS

AF:

0.269

Gnomad FIN

AF:

0.218

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.142

GnomAD3 exomes

AF:

0.180

AC:

44885

AN:

249134

Hom.:

4506

AF XY:

0.184

AC XY:

24728

AN XY:

134740

show subpopulations

Gnomad AFR exome

AF:

0.0825

Gnomad AMR exome

AF:

0.178

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.286

Gnomad SAS exome

AF:

0.256

Gnomad FIN exome

AF:

0.216

Gnomad NFE exome

AF:

0.154

Gnomad OTH exome

AF:

0.177

GnomAD4 exome

AF:

0.166

AC:

239860

AN:

1447628

Hom.:

21522

Cov.:

AF XY:

0.169

AC XY:

121319

AN XY:

719980

show subpopulations

Gnomad4 AFR exome

AF:

0.0808

Gnomad4 AMR exome

AF:

0.175

Gnomad4 ASJ exome

AF:

0.140

Gnomad4 EAS exome

AF:

0.332

Gnomad4 SAS exome

AF:

0.255

Gnomad4 FIN exome

AF:

0.211

Gnomad4 NFE exome

AF:

0.153

Gnomad4 OTH exome

AF:

0.167

GnomAD4 genome

AF:

0.148

AC:

22551

AN:

152200

Hom.:

1895

Cov.:

AF XY:

0.156

AC XY:

11572

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0853

Gnomad4 AMR

AF:

0.156

Gnomad4 ASJ

AF:

0.135

Gnomad4 EAS

AF:

0.292

Gnomad4 SAS

AF:

0.268

Gnomad4 FIN

AF:

0.218

Gnomad4 NFE

AF:

0.155

Gnomad4 OTH

AF:

0.141

Alfa

AF:

0.152

Hom.:

3197

Bravo

AF:

0.138

Asia WGS

AF:

0.265

AC:

920

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

4.5

DANN

Benign

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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