dbSNP rs141397961: RELN:c.9370-13_9370-8delATGTTT (chr7-103492033-CAAACAT-C) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_005045.4(RELN):c.9370-13_9370-8delATGTTT variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00291 in 1,605,952 control chromosomes in the GnomAD database, including 113 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 56 hom., cov: 31)

Exomes 𝑓: 0.0016 ( 57 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: 5.08

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 -16 ACMG points.

BP6

Variant 7-103492033-CAAACAT-C is Benign according to our data. Variant chr7-103492033-CAAACAT-C is described in ClinVar as [Benign]. Clinvar id is 95238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-103492033-CAAACAT-C is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RELN	NM_005045.4 link	c.9370-13_9370-8delATGTTT	splice_region_variant, intron_variant	Intron 57 of 64	ENST00000428762.6	NP_005036.2	P78509-1
RELN	NM_173054.3 link	c.9370-13_9370-8delATGTTT	splice_region_variant, intron_variant	Intron 57 of 63		NP_774959.1	P78509-2
SLC26A5-AS1	NR_110141.1 link	n.1366-12365_1366-12360delTAAACA	intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6 link	c.9370-13_9370-8delATGTTT		splice_region_variant, intron_variant	Intron 57 of 64	5	NM_005045.4	ENSP00000392423.1		P78509-1

Frequencies

GnomAD3 genomes

AF:

0.0150

AC:

2283

AN:

152020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0512

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00740

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.00908

GnomAD3 exomes

AF:

0.00394

AC:

976

AN:

247494

Hom.:

AF XY:

0.00299

AC XY:

400

AN XY:

133686

show subpopulations

Gnomad AFR exome

AF:

0.0523

Gnomad AMR exome

AF:

0.00324

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000200

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000223

Gnomad OTH exome

AF:

0.00198

GnomAD4 exome

AF:

0.00164

AC:

2379

AN:

1453814

Hom.:

AF XY:

0.00135

AC XY:

978

AN XY:

723450

show subpopulations

Gnomad4 AFR exome

AF:

0.0533

Gnomad4 AMR exome

AF:

0.00407

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000140

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000150

Gnomad4 OTH exome

AF:

0.00383

GnomAD4 genome

AF:

0.0150

AC:

2288

AN:

152138

Hom.:

Cov.:

AF XY:

0.0147

AC XY:

1093

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0512

Gnomad4 AMR

AF:

0.00739

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.00899

Alfa

AF:

0.00740

Hom.:

Bravo

AF:

0.0176

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Apr 22, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

May 03, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

RELN-related disorder

Benign:1

Aug 07, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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