rs13223714

Variant names:

• chr7-103849973-T-C
• rs13223714
• NM_005045.4:c.338-16301A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-103849973-T-C
• chr7-103849973-T-G

Variant summary

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

The NM_005045.4(RELN):​c.338-16301A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,066 control chromosomes in the GnomAD database, including 7,383 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 0.30 (7383 hom., cov: 32)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 0 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RELN	NM_005045.4	c.338-16301A>G		intron_variant	Intron 2 of 64	ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.338-16301A>G		intron_variant	Intron 2 of 63		NP_774959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.338-16301A>G		intron_variant	Intron 2 of 64	5	NM_005045.4	ENSP00000392423.1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45688 AN: 151948 Hom.: 7359 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.301 AC: 45775 AN: 152066 Hom.: 7383 Cov.: 32 AF XY: 0.308 AC XY: 22862 AN XY: 74336

African (AFR) AF: 0.318 AC: 13187 AN: 41458

American (AMR) AF: 0.304 AC: 4641 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 815 AN: 3468

East Asian (EAS) AF: 0.622 AC: 3212 AN: 5164

South Asian (SAS) AF: 0.558 AC: 2683 AN: 4810

European-Finnish (FIN) AF: 0.262 AC: 2770 AN: 10584

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17611 AN: 67978

Other (OTH) AF: 0.289 AC: 610 AN: 2108

Alfa AF: 0.279 Hom.: 26374

Bravo AF: 0.299

Asia WGS AF: 0.543 AC: 1888 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.30
DANN	Benign	0.44
PhyloP100		-1.1
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: rs13223714; hg19: chr7-103490420;