7-103734819-C-T

Variant names:

• chr7-103734819-C-T
• rs10487166
• NM_005045.4:c.657-6612G>A

Variant summary

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

The NM_005045.4(RELN):​c.657-6612G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,152 control chromosomes in the GnomAD database, including 945 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 0.11 (945 hom., cov: 32)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.741
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.18 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.657-6612G>A		intron	N/A	NP_005036.2
	RELN	NM_173054.3		c.657-6612G>A		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.657-6612G>A		intron	N/A	ENSP00000392423.1
	RELN	ENST00000424685.3	TSL:5	c.657-6612G>A		intron	N/A	ENSP00000388446.3
	RELN	ENST00000343529.9	TSL:5	c.657-6612G>A		intron	N/A	ENSP00000345694.5

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16654 AN: 152034 Hom.: 949 Cov.: 32

Gnomad AFR AF: 0.0935

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.0778

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.109 AC: 16648 AN: 152152 Hom.: 945 Cov.: 32 AF XY: 0.110 AC XY: 8175 AN XY: 74392

African (AFR) AF: 0.0933 AC: 3872 AN: 41514

American (AMR) AF: 0.117 AC: 1783 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 468 AN: 3470

East Asian (EAS) AF: 0.118 AC: 612 AN: 5184

South Asian (SAS) AF: 0.190 AC: 917 AN: 4814

European-Finnish (FIN) AF: 0.0778 AC: 824 AN: 10594

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7843 AN: 67996

Other (OTH) AF: 0.113 AC: 238 AN: 2114

Alfa AF: 0.0846 Hom.: 190

Bravo AF: 0.110

Asia WGS AF: 0.164 AC: 571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.0
DANN	Benign	0.49
PhyloP100		-0.74
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: rs10487166; hg19: chr7-103375266;