Variant 7-103989356-TGCCGCCGCCGCCGCC-TGCCGCCGCCGCC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_005045.4(RELN):c.-3_-1delGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,396,900 control chromosomes in the GnomAD database, including 35 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., cov: 0)

Exomes 𝑓: 0.0017 ( 34 hom. )

Consequence

RELN
NM_005045.4 5_prime_UTR

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 2.06

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 7-103989356-TGCC-T is Benign according to our data. Variant chr7-103989356-TGCC-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 358429.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=2}. Variant chr7-103989356-TGCC-T is described in Lovd as [Likely_benign]. Variant chr7-103989356-TGCC-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00159 (236/148362) while in subpopulation EAS AF= 0.00404 (19/4698). AF 95% confidence interval is 0.00265. There are 1 homozygotes in gnomad4. There are 120 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 34 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RELN	NM_005045.4 link	c.-3_-1delGGC		5_prime_UTR_variant	1/65	ENST00000428762.6	NP_005036.2	P78509-1
RELN	NM_173054.3 link	c.-3_-1delGGC		5_prime_UTR_variant	1/64		NP_774959.1	P78509-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6 link	c.-3_-1delGGC		5_prime_UTR_variant	1/65	5	NM_005045.4	ENSP00000392423.1		P78509-1

Frequencies

GnomAD3 genomes

AF:

0.00158

AC:

234

AN:

148264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00308

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00220

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00403

Gnomad SAS

AF:

0.00149

Gnomad FIN

AF:

0.000298

Gnomad MID

AF:

0.00676

Gnomad NFE

AF:

0.000643

Gnomad OTH

AF:

0.00147

GnomAD3 exomes

AF:

0.0113

AC:

720

AN:

63892

Hom.:

AF XY:

0.00989

AC XY:

366

AN XY:

37010

show subpopulations

Gnomad AFR exome

AF:

0.0245

Gnomad AMR exome

AF:

0.0187

Gnomad ASJ exome

AF:

0.0115

Gnomad EAS exome

AF:

0.0303

Gnomad SAS exome

AF:

0.00863

Gnomad FIN exome

AF:

0.00695

Gnomad NFE exome

AF:

0.00926

Gnomad OTH exome

AF:

0.0149

GnomAD4 exome

AF:

0.00168

AC:

2097

AN:

1248538

Hom.:

AF XY:

0.00170

AC XY:

1043

AN XY:

614850

show subpopulations

Gnomad4 AFR exome

AF:

0.00466

Gnomad4 AMR exome

AF:

0.00711

Gnomad4 ASJ exome

AF:

0.00338

Gnomad4 EAS exome

AF:

0.00296

Gnomad4 SAS exome

AF:

0.00267

Gnomad4 FIN exome

AF:

0.00132

Gnomad4 NFE exome

AF:

0.00134

Gnomad4 OTH exome

AF:

0.00256

GnomAD4 genome

AF:

0.00159

AC:

236

AN:

148362

Hom.:

Cov.:

AF XY:

0.00166

AC XY:

120

AN XY:

72350

show subpopulations

Gnomad4 AFR

AF:

0.00308

Gnomad4 AMR

AF:

0.00219

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00404

Gnomad4 SAS

AF:

0.00128

Gnomad4 FIN

AF:

0.000298

Gnomad4 NFE

AF:

0.000643

Gnomad4 OTH

AF:

0.00340

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2023	RELN: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Lissencephaly, Recessive

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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