Variant 7-103535518-C-T 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.7181-34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 1,588,700 control chromosomes in the GnomAD database, including 457,478 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 42690 hom., cov: 32)

Exomes 𝑓: 0.76 ( 414788 hom. )

Consequence

RELN
NM_005045.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.117

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:

LOC105375435 (HGNC:):

LOC105375435 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=-0.82).

BP6

Variant 7-103535518-C-T is Benign according to our data. Variant chr7-103535518-C-T is described in ClinVar as [Benign]. Clinvar id is 259612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RELN	NM_005045.4 link	c.7181-34G>A	intron_variant	Intron 45 of 64	ENST00000428762.6	NP_005036.2	P78509-1
RELN	NM_173054.3 link	c.7181-34G>A	intron_variant	Intron 45 of 63		NP_774959.1	P78509-2
LOC105375435	XR_001745315.2 link	n.41+888C>T	intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6 link	c.7181-34G>A		intron_variant	Intron 45 of 64	5	NM_005045.4	ENSP00000392423.1		P78509-1

Frequencies

GnomAD3 genomes

AF:

0.749

AC:

113872

AN:

152020

Hom.:

42653

Cov.:

show subpopulations

Gnomad AFR

AF:

0.751

Gnomad AMI

AF:

0.727

Gnomad AMR

AF:

0.751

Gnomad ASJ

AF:

0.767

Gnomad EAS

AF:

0.607

Gnomad SAS

AF:

0.681

Gnomad FIN

AF:

0.751

Gnomad MID

AF:

0.766

Gnomad NFE

AF:

0.762

Gnomad OTH

AF:

0.758

GnomAD3 exomes

AF:

0.743

AC:

185329

AN:

249508

Hom.:

69246

AF XY:

0.741

AC XY:

99966

AN XY:

134936

show subpopulations

Gnomad AFR exome

AF:

0.751

Gnomad AMR exome

AF:

0.769

Gnomad ASJ exome

AF:

0.766

Gnomad EAS exome

AF:

0.611

Gnomad SAS exome

AF:

0.698

Gnomad FIN exome

AF:

0.753

Gnomad NFE exome

AF:

0.763

Gnomad OTH exome

AF:

0.745

GnomAD4 exome

AF:

0.759

AC:

1089972

AN:

1436562

Hom.:

414788

Cov.:

AF XY:

0.756

AC XY:

541901

AN XY:

716444

show subpopulations

Gnomad4 AFR exome

AF:

0.752

Gnomad4 AMR exome

AF:

0.767

Gnomad4 ASJ exome

AF:

0.766

Gnomad4 EAS exome

AF:

0.577

Gnomad4 SAS exome

AF:

0.700

Gnomad4 FIN exome

AF:

0.753

Gnomad4 NFE exome

AF:

0.770

Gnomad4 OTH exome

AF:

0.751

GnomAD4 genome

AF:

0.749

AC:

113971

AN:

152138

Hom.:

42690

Cov.:

AF XY:

0.746

AC XY:

55445

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.751

Gnomad4 AMR

AF:

0.751

Gnomad4 ASJ

AF:

0.767

Gnomad4 EAS

AF:

0.607

Gnomad4 SAS

AF:

0.681

Gnomad4 FIN

AF:

0.751

Gnomad4 NFE

AF:

0.762

Gnomad4 OTH

AF:

0.758

Alfa

AF:

0.758

Hom.:

8989

Bravo

AF:

0.751

Asia WGS

AF:

0.647

AC:

2251

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 19, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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

-0.82

CADD

Benign

1.3

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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