7-103569621-A-G

Position:

• chr7-103569621-A-G

Variant summary

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

The NM_005045.4(RELN):​c.4588+2563T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,132 control chromosomes in the GnomAD database, including 5,631 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 0.25 (5631 hom., cov: 32)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RELN	NM_005045.4	c.4588+2563T>C		intron_variant		ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.4588+2563T>C		intron_variant			NP_774959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.4588+2563T>C		intron_variant		5	NM_005045.4	ENSP00000392423.1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38388 AN: 152014 Hom.: 5627 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.252 AC: 38385 AN: 152132 Hom.: 5631 Cov.: 32 AF XY: 0.252 AC XY: 18743 AN XY: 74372

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.408

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.257

Alfa AF: 0.318 Hom.: 10874

Bravo AF: 0.239

Asia WGS AF: 0.247 AC: 861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs362732; hg19: chr7-103210068;