rs2249372

Variant names:

• chr7-103597763-A-G
• rs2249372
• NM_005045.4:c.3334-1102T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-103597763-A-G
• chr7-103597763-A-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.3334-1102T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 152,100 control chromosomes in the GnomAD database, including 43,614 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 0.75 (43614 hom., cov: 32)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.878 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELN	NM_005045.4	MANE Select	c.3334-1102T>C		intron	N/A	NP_005036.2
	RELN	NM_173054.3		c.3334-1102T>C		intron	N/A	NP_774959.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELN	ENST00000428762.6	TSL:5 MANE Select	c.3334-1102T>C		intron	N/A	ENSP00000392423.1
	RELN	ENST00000424685.3	TSL:5	c.3334-1102T>C		intron	N/A	ENSP00000388446.3
	RELN	ENST00000343529.9	TSL:5	c.3334-1102T>C		intron	N/A	ENSP00000345694.5

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114152 AN: 151982 Hom.: 43562 Cov.: 32

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.710

Gnomad OTH AF: 0.758

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

GnomAD4 genome AF: 0.751 AC: 114257 AN: 152100 Hom.: 43614 Cov.: 32 AF XY: 0.747 AC XY: 55545 AN XY: 74344

African (AFR) AF: 0.886 AC: 36782 AN: 41520

American (AMR) AF: 0.667 AC: 10178 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 2476 AN: 3470

East Asian (EAS) AF: 0.738 AC: 3815 AN: 5170

South Asian (SAS) AF: 0.751 AC: 3619 AN: 4816

European-Finnish (FIN) AF: 0.638 AC: 6732 AN: 10558

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.710 AC: 48238 AN: 67982

Other (OTH) AF: 0.758 AC: 1603 AN: 2114

Alfa AF: 0.740 Hom.: 6378

Bravo AF: 0.762

Asia WGS AF: 0.725 AC: 2520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.65
PhyloP100		0.26
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: rs2249372; hg19: chr7-103238210;