rs563264

Positions:

• chr7-103726145-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.753+1966T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,236 control chromosomes in the GnomAD database, including 1,164 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 0.12 (1164 hom., cov: 32)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RELN	NM_005045.4	c.753+1966T>C		intron_variant		ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.753+1966T>C		intron_variant			NP_774959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.753+1966T>C		intron_variant		5	NM_005045.4	ENSP00000392423.1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17938 AN: 152118 Hom.: 1162 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.0997

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0269

Gnomad SAS AF: 0.0712

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.118 AC: 17948 AN: 152236 Hom.: 1164 Cov.: 32 AF XY: 0.117 AC XY: 8729 AN XY: 74426

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.0994

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.0268

Gnomad4 SAS AF: 0.0721

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.144

Alfa AF: 0.127 Hom.: 650

Bravo AF: 0.119

Asia WGS AF: 0.0550 AC: 192 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.0
DANN	Benign	0.58

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: rs563264; hg19: chr7-103366592;