rs362814

Positions:

• chr7-103574673-T-A
• chr7-103574673-T-C

Variant summary

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

The NM_005045.4(RELN):​c.4304-374A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 151,624 control chromosomes in the GnomAD database, including 42,368 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 0.74 (42368 hom., cov: 28)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RELN	NM_005045.4	c.4304-374A>T		intron_variant		ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.4304-374A>T		intron_variant			NP_774959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.4304-374A>T		intron_variant		5	NM_005045.4	ENSP00000392423	P5

Frequencies

GnomAD3 genomes AF: 0.745 AC: 112818 AN: 151506 Hom.: 42335 Cov.: 28

Gnomad AFR AF: 0.834

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.765

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

GnomAD4 genome AF: 0.745 AC: 112900 AN: 151624 Hom.: 42368 Cov.: 28 AF XY: 0.740 AC XY: 54814 AN XY: 74024

Gnomad4 AFR AF: 0.833

Gnomad4 AMR AF: 0.696

Gnomad4 ASJ AF: 0.731

Gnomad4 EAS AF: 0.659

Gnomad4 SAS AF: 0.735

Gnomad4 FIN AF: 0.638

Gnomad4 NFE AF: 0.727

Gnomad4 OTH AF: 0.763

Alfa AF: 0.729 Hom.: 5075

Bravo AF: 0.754

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.013
DANN	Benign	0.55

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: rs362814; hg19: chr7-103215120;