rs17133096

Positions:

• chr7-103797038-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005045.4(RELN):​c.474-20411T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0658 in 152,098 control chromosomes in the GnomAD database, including 596 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 0.066 (596 hom., cov: 32)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.357

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RELN	NM_005045.4	c.474-20411T>A		intron_variant		ENST00000428762.6
RELN	NM_173054.3	c.474-20411T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RELN	ENST00000428762.6	c.474-20411T>A		intron_variant		5	NM_005045.4	P5

Frequencies

GnomAD3 genomes AF: 0.0657 AC: 9992 AN: 151980 Hom.: 599 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0382

Gnomad ASJ AF: 0.0311

Gnomad EAS AF: 0.0347

Gnomad SAS AF: 0.00807

Gnomad FIN AF: 0.00634

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0319

Gnomad OTH AF: 0.0549

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

GnomAD4 genome AF: 0.0658 AC: 10003 AN: 152098 Hom.: 596 Cov.: 32 AF XY: 0.0619 AC XY: 4605 AN XY: 74366

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.0382

Gnomad4 ASJ AF: 0.0311

Gnomad4 EAS AF: 0.0346

Gnomad4 SAS AF: 0.00807

Gnomad4 FIN AF: 0.00634

Gnomad4 NFE AF: 0.0319

Gnomad4 OTH AF: 0.0543

Alfa AF: 0.0547 Hom.: 45

Bravo AF: 0.0715

Asia WGS AF: 0.0290 AC: 102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.22

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

Publications

LitVar

Other links and lift over

dbSNP: rs17133096; hg19: chr7-103437485;