rs3819479

Variant names:

• chr7-103756635-T-A
• rs3819479
• NM_005045.4:c.545-3421A>T

Your query was ambiguous. Multiple possible variants found:

• chr7-103756635-T-A
• chr7-103756635-T-C
• chr7-103756635-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.545-3421A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,092 control chromosomes in the GnomAD database, including 4,298 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 0.23 (4298 hom., cov: 32)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87
• 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: 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 (SAS) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RELN	NM_005045.4	c.545-3421A>T		intron_variant	Intron 4 of 64	ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.545-3421A>T		intron_variant	Intron 4 of 63		NP_774959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.545-3421A>T		intron_variant	Intron 4 of 64	5	NM_005045.4	ENSP00000392423.1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35680 AN: 151976 Hom.: 4298 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.235 AC: 35713 AN: 152092 Hom.: 4298 Cov.: 32 AF XY: 0.235 AC XY: 17466 AN XY: 74350

African (AFR) AF: 0.253 AC: 10511 AN: 41490

American (AMR) AF: 0.243 AC: 3715 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 867 AN: 3470

East Asian (EAS) AF: 0.196 AC: 1012 AN: 5172

South Asian (SAS) AF: 0.290 AC: 1398 AN: 4820

European-Finnish (FIN) AF: 0.202 AC: 2128 AN: 10560

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15191 AN: 67996

Other (OTH) AF: 0.245 AC: 518 AN: 2112

Alfa AF: 0.104 Hom.: 154

Bravo AF: 0.238

Asia WGS AF: 0.237 AC: 820 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.32
DANN	Benign	0.52
PhyloP100		-1.9
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: rs3819479; hg19: chr7-103397082;