rs499953

chr7-103757219-G-T

Variant summary

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

The NM_005045.4(RELN):c.545-4005C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 151,910 control chromosomes in the GnomAD database, including 24,039 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 0.54 (24039 hom., cov: 32)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.173

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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RELN	NM_005045.4	c.545-4005C>A		intron_variant		ENST00000428762.6
RELN	NM_173054.3	c.545-4005C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RELN	ENST00000428762.6	c.545-4005C>A		intron_variant		5	NM_005045.4	P5

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82334 AN: 151794 Hom.: 24043 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.595

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

GnomAD4 genome AF: 0.542 AC: 82331 AN: 151910 Hom.: 24039 Cov.: 32 AF XY: 0.537 AC XY: 39893 AN XY: 74264

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.610

Gnomad4 NFE AF: 0.669

Gnomad4 OTH AF: 0.588

Alfa AF: 0.639 Hom.: 41948

Bravo AF: 0.529

Asia WGS AF: 0.408 AC: 1419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	4.9
Dann	Benign	0.70

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: rs499953; hg19: chr7-103397666;