rs7341475

Variant names:

• chr7-103764368-G-A
• rs7341475
• NM_005045.4:c.545-11154C>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.545-11154C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,026 control chromosomes in the GnomAD database, including 2,424 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 0.17 (2424 hom., cov: 31)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.617
• Publications: 73 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 (AMR) allele frequency at 95% confidence interval = 0.21 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.545-11154C>T		intron	N/A	NP_005036.2
	RELN	NM_173054.3		c.545-11154C>T		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.545-11154C>T		intron	N/A	ENSP00000392423.1
	RELN	ENST00000424685.3	TSL:5	c.545-11154C>T		intron	N/A	ENSP00000388446.3
	RELN	ENST00000343529.9	TSL:5	c.545-11154C>T		intron	N/A	ENSP00000345694.5

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26298 AN: 151908 Hom.: 2427 Cov.: 31

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.0715

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.173 AC: 26301 AN: 152026 Hom.: 2424 Cov.: 31 AF XY: 0.175 AC XY: 12990 AN XY: 74298

African (AFR) AF: 0.166 AC: 6889 AN: 41486

American (AMR) AF: 0.216 AC: 3297 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 732 AN: 3468

East Asian (EAS) AF: 0.0717 AC: 369 AN: 5150

South Asian (SAS) AF: 0.116 AC: 558 AN: 4802

European-Finnish (FIN) AF: 0.227 AC: 2396 AN: 10558

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11316 AN: 67988

Other (OTH) AF: 0.212 AC: 446 AN: 2108

Alfa AF: 0.170 Hom.: 7877

Bravo AF: 0.178

Asia WGS AF: 0.100 AC: 347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.50
PhyloP100		0.62
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: rs7341475; hg19: chr7-103404815;