rs39327

Positions:

• chr7-103804224-G-A

Variant summary

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

The NM_005045.4(RELN):​c.474-27597C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 151,960 control chromosomes in the GnomAD database, including 4,210 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 0.23 (4210 hom., cov: 33)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RELN	NM_005045.4	c.474-27597C>T		intron_variant		ENST00000428762.6
RELN	NM_173054.3	c.474-27597C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RELN	ENST00000428762.6	c.474-27597C>T		intron_variant		5	NM_005045.4	P5

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34210 AN: 151842 Hom.: 4214 Cov.: 33

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.0745

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.225 AC: 34215 AN: 151960 Hom.: 4210 Cov.: 33 AF XY: 0.224 AC XY: 16668 AN XY: 74296

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.0745

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.240

Alfa AF: 0.194 Hom.: 1392

Bravo AF: 0.237

Asia WGS AF: 0.113 AC: 394 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.5
DANN	Benign	0.44

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: rs39327; hg19: chr7-103444671;