rs634500

Positions:

• chr7-103750962-T-C

Variant summary

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

The NM_005045.4(RELN):​c.578-1458A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 152,072 control chromosomes in the GnomAD database, including 32,643 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 0.65 (32643 hom., cov: 32)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.143

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RELN	NM_005045.4	c.578-1458A>G		intron_variant		ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.578-1458A>G		intron_variant			NP_774959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.578-1458A>G		intron_variant		5	NM_005045.4	ENSP00000392423	P5

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98202 AN: 151954 Hom.: 32589 Cov.: 32

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.647 AC: 98318 AN: 152072 Hom.: 32643 Cov.: 32 AF XY: 0.640 AC XY: 47595 AN XY: 74320

Gnomad4 AFR AF: 0.812

Gnomad4 AMR AF: 0.581

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.567

Gnomad4 SAS AF: 0.566

Gnomad4 FIN AF: 0.530

Gnomad4 NFE AF: 0.595

Gnomad4 OTH AF: 0.656

Alfa AF: 0.603 Hom.: 57365

Bravo AF: 0.659

Asia WGS AF: 0.546 AC: 1896 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.6
DANN	Benign	0.37

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: rs634500; hg19: chr7-103391409;