rs2299383

Positions:

• chr7-103778399-C-T

Variant summary

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

The NM_005045.4(RELN):​c.474-1772G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 152,004 control chromosomes in the GnomAD database, including 13,256 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 0.42 (13256 hom., cov: 32)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RELN	NM_005045.4	c.474-1772G>A		intron_variant		ENST00000428762.6
RELN	NM_173054.3	c.474-1772G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RELN	ENST00000428762.6	c.474-1772G>A		intron_variant		5	NM_005045.4	P5

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63214 AN: 151884 Hom.: 13254 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.416 AC: 63239 AN: 152004 Hom.: 13256 Cov.: 32 AF XY: 0.417 AC XY: 30996 AN XY: 74290

Gnomad4 AFR AF: 0.378

Gnomad4 AMR AF: 0.404

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.498

Gnomad4 FIN AF: 0.467

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.425

Alfa AF: 0.430 Hom.: 6704

Bravo AF: 0.413

Asia WGS AF: 0.428 AC: 1487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.63
DANN	Benign	0.82

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: rs2299383; hg19: chr7-103418846;