rs362814

Variant names:

• chr7-103574673-T-A
• rs362814
• NM_005045.4:c.4304-374A>T

Your query was ambiguous. Multiple possible variants found:

• chr7-103574673-T-A
• chr7-103574673-T-C

Variant summary

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

The NM_005045.4(RELN):​c.4304-374A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 151,624 control chromosomes in the GnomAD database, including 42,368 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 0.74 (42368 hom., cov: 28)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344
• Publications: 4 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: PanelApp Australia, Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae), G2P, Orphanet
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005045.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELN	NM_005045.4	MANE Select	c.4304-374A>T		intron	N/A	NP_005036.2
	RELN	NM_173054.3		c.4304-374A>T		intron	N/A	NP_774959.1	P78509-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELN	ENST00000428762.6	TSL:5 MANE Select	c.4304-374A>T		intron	N/A	ENSP00000392423.1	P78509-1
	RELN	ENST00000424685.3	TSL:5	c.4304-374A>T		intron	N/A	ENSP00000388446.3	J3KQ66
	RELN	ENST00000343529.9	TSL:5	c.4304-374A>T		intron	N/A	ENSP00000345694.5	P78509-2

Frequencies

GnomAD3 genomes AF: 0.745 AC: 112818 AN: 151506 Hom.: 42335 Cov.: 28

Gnomad AFR AF: 0.834

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.765

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

GnomAD4 genome AF: 0.745 AC: 112900 AN: 151624 Hom.: 42368 Cov.: 28 AF XY: 0.740 AC XY: 54814 AN XY: 74024

African (AFR) AF: 0.833 AC: 34460 AN: 41346

American (AMR) AF: 0.696 AC: 10607 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.731 AC: 2532 AN: 3462

East Asian (EAS) AF: 0.659 AC: 3380 AN: 5126

South Asian (SAS) AF: 0.735 AC: 3510 AN: 4778

European-Finnish (FIN) AF: 0.638 AC: 6670 AN: 10458

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.727 AC: 49340 AN: 67914

Other (OTH) AF: 0.763 AC: 1594 AN: 2088

Alfa AF: 0.729 Hom.: 5075

Bravo AF: 0.754

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.013
DANN	Benign	0.55
PhyloP100		-0.34
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: rs362814; hg19: chr7-103215120;