rs74952625

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1

The NM_005045.4(RELN):c.8120-9T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000313 in 1,609,420 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

RELN
NM_005045.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0005777

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.482

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.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 7-103511014-A-G is Benign according to our data. Variant chr7-103511014-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 197926.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00168 (256/152312) while in subpopulation AFR AF= 0.00592 (246/41560). AF 95% confidence interval is 0.00531. There are 1 homozygotes in gnomad4. There are 108 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
RELN	NM_005045.4 linkuse as main transcript	c.8120-9T>C	splice_polypyrimidine_tract_variant, intron_variant	ENST00000428762.6
SLC26A5-AS1	NR_110141.1 linkuse as main transcript	n.1487-1755A>G	intron_variant, non_coding_transcript_variant
RELN	NM_173054.3 linkuse as main transcript	c.8120-9T>C	splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RELN	ENST00000428762.6 linkuse as main transcript	c.8120-9T>C		splice_polypyrimidine_tract_variant, intron_variant		5	NM_005045.4	P5	P78509-1
SLC26A5-AS1	ENST00000422488.1 linkuse as main transcript	n.1487-1755A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00169

AC:

257

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00596

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000561

AC:

140

AN:

249430

Hom.:

AF XY:

0.000326

AC XY:

AN XY:

134790

show subpopulations

Gnomad AFR exome

AF:

0.00772

Gnomad AMR exome

AF:

0.000408

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000170

AC:

247

AN:

1457108

Hom.:

Cov.:

AF XY:

0.000143

AC XY:

104

AN XY:

725068

show subpopulations

Gnomad4 AFR exome

AF:

0.00630

Gnomad4 AMR exome

AF:

0.000336

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000349

GnomAD4 genome

AF:

0.00168

AC:

256

AN:

152312

Hom.:

Cov.:

AF XY:

0.00145

AC XY:

108

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00592

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000651

Hom.:

Bravo

AF:

0.00194

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Dec 31, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 14, 2015	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 27, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 24, 2021

- -

RELN-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 10, 2021

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

BayesDel_noAF

Benign

-0.78

Cadd

Benign

7.5

Dann

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00058

dbscSNV1_RF

Benign

0.20

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