7-103565554-GAA-GA

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_005045.4(RELN):c.4937-4delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00741 in 1,295,968 control chromosomes in the GnomAD database, including 4 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 1 hom., cov: 0)

Exomes 𝑓: 0.0080 ( 3 hom. )

Consequence

RELN
NM_005045.4 splice_region, intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 0.186

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 -16 ACMG points.

BP6

Variant 7-103565554-GA-G is Benign according to our data. Variant chr7-103565554-GA-G is described in ClinVar as [Benign]. Clinvar id is 196903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-103565554-GA-G is described in Lovd as [Benign]. Variant chr7-103565554-GA-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0031 (458/147966) while in subpopulation AFR AF= 0.00965 (390/40396). AF 95% confidence interval is 0.00886. There are 1 homozygotes in gnomad4. There are 223 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RELN	NM_005045.4 link	c.4937-4delT		splice_region_variant, intron_variant	Intron 33 of 64	ENST00000428762.6	NP_005036.2	P78509-1
RELN	NM_173054.3 link	c.4937-4delT		splice_region_variant, intron_variant	Intron 33 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.4937-4delT		splice_region_variant, intron_variant	Intron 33 of 64	5	NM_005045.4	ENSP00000392423.1		P78509-1

Frequencies

GnomAD3 genomes

AF:

0.00309

AC:

457

AN:

147892

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00101

Gnomad ASJ

AF:

0.000584

Gnomad EAS

AF:

0.000788

Gnomad SAS

AF:

0.000212

Gnomad FIN

AF:

0.000631

Gnomad MID

AF:

0.00325

Gnomad NFE

AF:

0.000524

Gnomad OTH

AF:

0.00196

GnomAD4 exome

AF:

0.00797

AC:

9144

AN:

1148002

Hom.:

Cov.:

AF XY:

0.00816

AC XY:

4640

AN XY:

568786

show subpopulations

Gnomad4 AFR exome

AF:

0.0204

Gnomad4 AMR exome

AF:

0.0216

Gnomad4 ASJ exome

AF:

0.00881

Gnomad4 EAS exome

AF:

0.0178

Gnomad4 SAS exome

AF:

0.0127

Gnomad4 FIN exome

AF:

0.0132

Gnomad4 NFE exome

AF:

0.00631

Gnomad4 OTH exome

AF:

0.00761

GnomAD4 genome

AF:

0.00310

AC:

458

AN:

147966

Hom.:

Cov.:

AF XY:

0.00310

AC XY:

223

AN XY:

71996

show subpopulations

Gnomad4 AFR

AF:

0.00965

Gnomad4 AMR

AF:

0.00101

Gnomad4 ASJ

AF:

0.000584

Gnomad4 EAS

AF:

0.000791

Gnomad4 SAS

AF:

0.000213

Gnomad4 FIN

AF:

0.000631

Gnomad4 NFE

AF:

0.000524

Gnomad4 OTH

AF:

0.00194

Alfa

AF:

0.0382

Hom.:

198

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jul 17, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Norman-Roberts syndrome;C4225327:Familial temporal lobe epilepsy 7

Benign:1

Jan 25, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Norman-Roberts syndrome

Benign:1

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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