rs362780

Variant names:

• chr7-103549911-G-A
• rs362780
• NM_005045.4:c.6302+1156C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005045.4(RELN):​c.6302+1156C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0887 in 152,208 control chromosomes in the GnomAD database, including 911 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.089 (911 hom., cov: 32)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• lissencephaly with cerebellar hypoplasia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Norman-Roberts syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P, PanelApp Australia
• familial temporal lobe epilepsy 7

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal dominant epilepsy with auditory features

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• ankylosing spondylitis

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RELN	NM_005045.4	c.6302+1156C>T		intron_variant	Intron 41 of 64	ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.6302+1156C>T		intron_variant	Intron 41 of 63		NP_774959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.6302+1156C>T		intron_variant	Intron 41 of 64	5	NM_005045.4	ENSP00000392423.1

Frequencies

GnomAD3 genomes AF: 0.0886 AC: 13475 AN: 152090 Hom.: 910 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0731

Gnomad ASJ AF: 0.0695

Gnomad EAS AF: 0.0826

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0259

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0392

Gnomad OTH AF: 0.0856

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0887 AC: 13507 AN: 152208 Hom.: 911 Cov.: 32 AF XY: 0.0890 AC XY: 6626 AN XY: 74408

African (AFR) AF: 0.190 AC: 7882 AN: 41498

American (AMR) AF: 0.0733 AC: 1122 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0695 AC: 241 AN: 3470

East Asian (EAS) AF: 0.0826 AC: 428 AN: 5182

South Asian (SAS) AF: 0.137 AC: 660 AN: 4820

European-Finnish (FIN) AF: 0.0259 AC: 274 AN: 10596

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0392 AC: 2666 AN: 68018

Other (OTH) AF: 0.0856 AC: 181 AN: 2114

Alfa AF: 0.0587 Hom.: 1245

Bravo AF: 0.0961

Asia WGS AF: 0.132 AC: 458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.28
DANN	Benign	0.63
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs362780; hg19: chr7-103190358;